MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Basic Research in Cardiology' source. Wed, 08 Feb 2012 09:32:29 +0100 http://www.medworm.com/index.php?rid=5659538&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F73g4682q7477j16u%2F In conclusion, PTEN is critically involved in post-MI remodeling through the Akt/IL-10 signaling pathway. Therefore, targeting PTEN may be an effective approach to post-MI remodeling. Content Type Journal ArticleCategory Original ContributionPages 1-15DOI 10.1007/s00395-012-0248-6Authors Nirmal Parajuli, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 333, Baltimore, MD 21205, USAYuan Yuan, Department of Cardiology, Forth Military Medical University Xijing Hospital, Xian, Shaanxi, ChinaXiaoxu Zheng, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 333, Baltimore, MD 21205, USADjahida Bedja, Department of Pathology, Johns Hopkins University Schoo... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5659538 Wed, 01 Feb 2012 17:09:57 +0100 5659538 http://www.medworm.com/index.php?rid=5619899&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu17478153331014n%2F Abstract  Primary chronic kidney disease is associated with high cardiovascular risk. However, the exact mechanisms behind this cardiorenal interaction remain unclear. We investigated the interaction between heart and kidneys in novel animal model for cardiorenal interaction. Normal Wistar rats and Munich Wistar Fromter rats, spontaneously developing renal dysfunction, were subjected to experimental myocardial infarction to induce cardiac dysfunction (CD) and combined cardiorenal dysfunction (CRD), respectively (N = 5–10). Twelve weeks later, cardiac- and renal parameters were evaluated. Cardiac, but not renal dysfunction was exaggerated in CRD. Accelerated cardiac dysfunction in CRD was indicated by decreased cardiac output (CD 109 ± 10 vs. CRD 79&nbs... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5619899 Thu, 19 Jan 2012 06:56:46 +0100 5619899 http://www.medworm.com/index.php?rid=5597180&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl036263j3k6gj734%2F In conclusion, the level of PKA-dependent TnI phosphorylation and the Ca2+ sensitivity of force production exhibited a high cell-to-cell variability at the LV pacing site, possibly explaining the abnormalities of the regional myocardial contractile function in a porcine model of pacing-induced HF. Content Type Journal ArticleCategory Original ContributionPages 1-13DOI 10.1007/s00395-012-0244-xAuthors Dániel Czuriga, Division of Clinical Physiology, Research Center for Molecular Medicine, Institute of Cardiology, Faculty of Medicine, University of Debrecen, Medical and Health Science Center, Móricz Zs. krt. 22, 4032 Debrecen, HungaryAttila Tóth, Division of Clinical Physiology, Research Center for Molecular Medicine, Institute of Cardiology, Faculty of Medicine, University of De... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5597180 Wed, 11 Jan 2012 17:55:57 +0100 5597180 http://www.medworm.com/index.php?rid=5597181&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq9603h22011n0475%2F Abstract  Epigenetics represents a phenomenon of altered heritable phenotypic expression of genetic information occurring without changes in DNA sequence. Epigenetic modifications control embryonic development, differentiation and stem cell (re)programming. These modifications can be affected by exogenous stimuli (e.g., diabetic milieu, smoking) and oftentimes culminate in disease initiation. DNA methylation has been studied extensively and represents a well-understood epigenetic mechanism. During this process cytosine residues preceding a guanosine in the DNA sequence are methylated. CpG-islands are short-interspersed DNA sequences with clusters of CG sequences. The abnormal methylation of CpG islands in the promoter region of genes leads to a silencing of genetic informati... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5597181 Tue, 10 Jan 2012 16:49:32 +0100 5597181 http://www.medworm.com/index.php?rid=5597182&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu0w1821vpp026752%2F Abstract  We have previously shown that remote ischemic preconditioning by limb ischemia (rIPC) or intra-arterial adenosine releases a dialyzable cardioprotective circulating factor(s), the release of which requires an intact neural connection to the limb and is blocked by pretreatment with S-nitroso-N-acetylpenicillamine (SNAP). Remote cardioprotection can be induced by other forms of peripheral stimulation including topical capsaicin, but the mechanisms of their signal transduction are incompletely understood. Rabbits were anesthetized by intravenous pentobarbital, intubated and ventilated, then randomized (4–7 animals in each group) to receive sham procedure, rIPC (4 cycles of 5 min lower limb ischemia, 5 min reperfusion), direct femoral nerve stimulation... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5597182 Mon, 09 Jan 2012 19:34:42 +0100 5597182 http://www.medworm.com/index.php?rid=5597183&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3331165u71767246%2F Abstract  Ossabaw miniswine have been naturally selected to efficiently store large amounts of lipids offering them a survival advantage. Our goal was to evaluate the myocardial response to chronic ischemia of the Ossabaw consuming a hypercaloric, high-fat/cholesterol diet with and without metformin supplementation. At 6 weeks of age animals were fed either a regular diet (OC, n = 9), a hypercaloric high-fat/cholesterol diet (OHC, n = 9), or a hypercaloric high-fat/cholesterol diet supplemented with metformin (OHCM, n = 8). At 9 weeks, all animals underwent ameroid constrictor placement to the left circumflex coronary artery to simulate chronic ischemia. Seven weeks after ameroid placement, all animals underwent hemodynamic and functiona... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5597183 Mon, 09 Jan 2012 19:34:41 +0100 5597183 http://www.medworm.com/index.php?rid=5559755&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh835x60h18668387%2F Abstract  Sustained increase of cardiac workload is known to trigger cardiac remodeling with eventual development of cardiac failure. Compelling evidence points to a critical role of enhanced cardiac Na+/H+ exchanger (NHE1) activity in the underlying pathophysiology. The signaling triggering up-regulation of NHE1 remained, however, ill defined. The present study explored the involvement of the serum- and glucocorticoid-inducible kinase Sgk1 in cardiac remodeling due to transverse aortic constriction (TAC). To this end, experiments were performed in gene targeted mice lacking functional Sgk1 (sgk1 −/−) and their wild-type controls (sgk1 +/+). Transcript levels have been determined by RT-PCR, cytosolic pH (pH i ) utilizing 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carbox... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5559755 Mon, 02 Jan 2012 16:51:03 +0100 5559755 http://www.medworm.com/index.php?rid=5552205&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu471686g32l43564%2F In conclusion, our results indicate that cFLIP protects against the development of post-infarction cardiac remodelling. Thus, cFLIP gene delivery shows promise as a clinically powerful and novel therapeutic strategy for the treatment of heart failure after MI. Content Type Journal ArticleCategory Original ContributionPages 1-21DOI 10.1007/s00395-011-0239-zAuthors Jinfeng Xiao, Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060 People’s Republic of ChinaMark Moon, Division of Cardiology, Heart and Stroke/Richard Lewar Centre of Excellence, University Health Network, University of Toronto, Toronto, ON M5S 3E2, CanadaLing Yan, Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060 People’s Republi... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5552205 Tue, 27 Dec 2011 17:04:23 +0100 5552205 http://www.medworm.com/index.php?rid=5544358&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr1u24x844051757w%2F In conclusion, this study is the first to demonstrate that DMD is associated with NO-mediated vascular endothelial dysfunction linked to an altered expression of eNOS and nNOS, which can be overcome by bradykinin. Content Type Journal ArticleCategory Original ContributionPages 1-9DOI 10.1007/s00395-011-0240-6Authors Hubert Dabiré, INSERM U955, 94000 Créteil, FranceInès Barthélémy, UPR de Neurobiologie, Ecole Nationale Vétérinaire d’Alfort, 94700 Maisons-Alfort, FranceNicolas Blanchard-Gutton, UPR de Neurobiologie, Ecole Nationale Vétérinaire d’Alfort, 94700 Maisons-Alfort, FranceLucien Sambin, INSERM U955, 94000 Créteil, FranceCarolina Carlos Sampedrano, INSERM U955, 94000 Créteil, FranceVassiliki Gouni, INSERM U955, 94000 Créteil, FranceYves Unterfinger, UPR de Neu... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5544358 Thu, 22 Dec 2011 12:50:32 +0100 5544358 http://www.medworm.com/index.php?rid=5544359&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fvl0492531h8701j3%2F Content Type Journal ArticleCategory ErratumPages 1-1DOI 10.1007/s00395-011-0234-4Authors Zhaohui Xu, Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, 1102 Bates Street, FC 430.09, Houston, TX 77030, USAMoreshwar Desai, Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, 1102 Bates Street, FC 430.09, Houston, TX 77030, USAJoseph Philip, Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, 1102 Bates Street, FC 430.09, Houston, TX 77030, USANatarajan Sivsubramanian, Department of Medicine, Winters Center for Heart Failure Research, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX, USANeil E. Bowles, Department of Pediatrics, Division of Cardiology, University of... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5544359 Wed, 21 Dec 2011 20:05:12 +0100 5544359 http://www.medworm.com/index.php?rid=5544362&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk03tx0501t149174%2F Abstract  Despite abundant clinical evidence linking metabolic abnormalities to diabetic vasculopathy, the molecular basis of individual susceptibility to diabetic vascular complications is still largely undetermined. Endothelial dysfunction in diabetes-associated vascular complications is considered an early stage of vasculopathy and has attracted considerable research interests. Type 2 diabetes is characterized by metabolic abnormalities, such as hyperglycemia, excess liberation of free fatty acids (FFA), insulin resistance and hyperinsulinemia. These abnormalities exert pathological impact on endothelial function by attenuating endothelium-mediated vasomotor function, enhancing endothelial apoptosis, stimulating endothelium activation/endothelium–monocyte adhesion, pro... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5544362 Wed, 21 Dec 2011 20:05:11 +0100 5544362 http://www.medworm.com/index.php?rid=5544361&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Funw388u0885015q3%2F Abstract  Persistent inflammatory responses participate in the pathogenesis of adverse ventricular remodeling after myocardial infarction (MI). We hypothesized that regulatory T (Treg) cells modulate inflammatory responses, attenuate ventricular remodeling and subsequently improve cardiac function after MI. Acute MI was induced by ligation of the left anterior descending coronary artery in rats. Infiltration of Foxp3+ Treg cells was detected in the infarcted heart. Expansion of Treg cells in vivo by means of adoptive transfer as well as a CD28 superagonistic antibody (JJ316) resulted in an increased number of Foxp3+ Treg cells in the infarcted heart. Subsequently, rats with MI showed improved cardiac function following Treg cells transfer or JJ316 injection. Interstitial fib... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5544361 Wed, 21 Dec 2011 20:05:11 +0100 5544361 http://www.medworm.com/index.php?rid=5544360&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F48g8181w0n300853%2F This study studied these pathways in two mouse models of HCM that mainly differ by the presence or absence of truncated mutant proteins. Analyses were performed in homozygous Mybpc3-targeted knock-in (KI) mice, carrying a HCM mutation and exhibiting low levels of mutant cardiac myosin-binding protein C (cMyBP-C), and in Mybpc3-targeted knock-out (KO) mice expressing no cMyBP-C, thus serving as a model of pure cMyBP-C insufficiency. In the early postnatal development of cardiac hypertrophy, both models showed higher levels of ubiquitinated proteins and greater proteasomal activities. To specifically monitor the degradation capacity of the UPS with age, mice were crossed with transgenic mice that overexpress UbG76V-GFP. UbG76V-GFP protein levels were fourfold higher in 1-year-old KI, b... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5544360 Wed, 21 Dec 2011 20:05:11 +0100 5544360 http://www.medworm.com/index.php?rid=5544363&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F32k1182t27370166%2F In conclusion, even in the presence of adrenergic-induced cardiomyocyte apoptosis, marked cardiac dilatation and pump dysfunction produced by chronic β-adrenergic receptor activation can be completely reversed by withdrawal of the excessive adrenergic stimulus. Content Type Journal ArticleCategory Original ContributionPages 1-12DOI 10.1007/s00395-011-0238-0Authors Hendrik L. Booysen, Cardiovascular Pathophysiology and Genomics Research Unit, Faculty of Health Sciences, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, Johannesburg, 2193 South AfricaGavin R. Norton, Cardiovascular Pathophysiology and Genomics Research Unit, Faculty of Health Sciences, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parkt... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5544363 Wed, 21 Dec 2011 20:05:09 +0100 5544363 http://www.medworm.com/index.php?rid=5515267&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr17272418h360524%2F Abstract  Pro-coagulant and pro-inflammatory intramyocardial (micro)vasculature plays an important role in acute myocardial infarction (AMI). Currently, inhibition of serine protease dipeptidyl peptidase 4 (DPP4) receives a lot of interest as an anti-hyperglycemic therapy in type 2 diabetes patients. However, DPP4 also possesses anti-thrombotic properties and may behave as an immobilized anti-coagulant on endothelial cells. Here, we studied the expression and activity of endothelial DPP4 in human myocardial infarction in relation to a prothrombogenic endothelial phenotype. Using (immuno)histochemistry, DPP4 expression and activity were found on the endothelium of intramyocardial blood vessels in autopsied control hearts (n = 9). Within the infarction area of AMI pa... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5515267 Tue, 13 Dec 2011 16:58:47 +0100 5515267 http://www.medworm.com/index.php?rid=5457250&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc2l8662r602x1677%2F Abstract  Recently, exercise has been recommended as a part of lifestyle modification for all hypertensive patients; however, the precise mechanisms of its effects on hypertension are largely unknown. Therefore, this study aimed to investigate the mechanisms within the brain that can influence exercise-induced effects in an animal model of human essential hypertension. Young normotensive WKY rats and SHR were given moderate-intensity exercise for 16 weeks. Blood pressure was measured bi-weekly by tail-cuff method. Animals were then euthanized; paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM), important cardiovascular regulatory centers in the brain, were collected and analyzed by real-time RT-PCR, Western blot, EIA, and fluorescent microscopy. Exe... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5457250 Mon, 28 Nov 2011 16:57:14 +0100 5457250 http://www.medworm.com/index.php?rid=5407575&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw2n553t527477785%2F Abstract  G-CSF (granulocyte colony-stimulating factor) treatment has been shown to cause beneficial effects including a reduction of inducible arrhythmias in rodent models of ischemic cardiomyopathy. The aim of the present study was to test whether these effects do also apply to pacing-induced non-ischemic heart failure. In 24 female rabbits, heart failure was induced by rapid ventricular pacing. 24 rabbits were sham operated. The paced rabbits developed a significant decrease of ejection fraction. 11 heart failure rabbits (CHF) and 11 sham-operated (S) rabbits served as controls, whereas 13 sham (S-G-CSF) and 13 heart failure rabbits (CHF-G-CSF) were treated with 10 μg/kg G-CSF s.c. over 17 ± 4 days. G-CSF treatment caused a ~25% increased arterial a... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5407575 Wed, 09 Nov 2011 17:58:21 +0100 5407575 http://www.medworm.com/index.php?rid=5386034&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F20t73076585243n8%2F Abstract  Despite the apparent appropriateness of left ventricular (LV) remodeling following myocardial infarction (MI), it poses an independent risk factor for development of heart failure. There is a paucity of studies into the molecular mechanisms of LV remodeling in large animal species. We took an unbiased molecular approach to identify candidate transcription factors (TFs) mediating the genetic reprogramming involved in post-MI LV remodeling in swine. Left ventricular tissue was collected from remote, non-infarcted myocardium, 3 weeks after MI-induction or sham-surgery. Microarray analysis identified 285 upregulated and 278 downregulated genes (FDR < 0.05). Of these differentially expressed genes, the promoter regions of the human homologs were searc... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5386034 Fri, 04 Nov 2011 16:50:56 +0100 5386034 http://www.medworm.com/index.php?rid=5335448&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg6l5705t1g071906%2F The objective of this study is to define and characterize the specific PDE isoform that is altered during cardiac fibroblast activation and functionally important for regulating myofibroblast activation and ECM synthesis. We have found that Ca2+/calmodulin-stimulated PDE1A isoform is specifically induced in activated cardiac myofibroblasts stimulated by Ang II and TGF-β in vitro as well as in vivo within fibrotic regions of mouse, rat, and human diseased hearts. Inhibition of PDE1A function via PDE1-selective inhibitor or PDE1A shRNA significantly reduced Ang II or TGF-β-induced myofibroblast activation, ECM synthesis, and pro-fibrotic gene expression in rat cardiac fibroblasts. Moreover, the PDE1 inhibitor attenuated isoproterenol-induced interstitial fibrosis in mice. Mechanistic... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5335448 Wed, 19 Oct 2011 15:46:31 +0100 5335448 http://www.medworm.com/index.php?rid=5323830&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb75430528v1h4l73%2F Abstract  Although mitochondria are key determinants of myocardial injury during ischemia–reperfusion (I/R), their interaction with critical cytoprotective signaling systems is not fully understood. Sphingosine-1-phosphate (S1P) produced by sphingosine kinase-1 protects the heart from I/R damage. Recently a new role for mitochondrial S1P produced by a second isoform of sphingosine kinase, SphK2, was described to regulate complex IV assembly and respiration via interaction with mitochondrial prohibitin-2. Here we investigated the role of SphK2 in cardioprotection by preconditioning. Littermate (WT) and sphk2 −/− mice underwent 45 min of in vivo ischemia and 24 h reperfusion. Mice received no intervention (I/R) or preconditioning (PC) via 5 min I/R before... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5323830 Sat, 15 Oct 2011 05:53:40 +0100 5323830 http://www.medworm.com/index.php?rid=5285368&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd25r4n6n12410332%2F Abstract  Heart rate reduction with the I(f)-channel-inhibitor ivabradine is a novel and appealing option in the therapy of patients with ischemic heart disease. The aim of the current study was to determine the effects of ivabradine in two different animal models of vascular disease characterized by increased oxidative stress and endothelial dysfunction. Wistar rats with angiotensin II induced hypertension and ApoE knockout mice were used as animal models of endothelial dysfunction and oxidative stress, with half of the animals receiving ivabradine 10 mg/kg/day in parallel. Ivabradine lead to a sustained 15–20% heart rate reduction, but had no effect on blood pressure. While ivabradine had no effect on endothelial function and vascular reactive oxygen species produc... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5285368 Sun, 02 Oct 2011 05:46:59 +0100 5285368 http://www.medworm.com/index.php?rid=5285369&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl404j8255x788306%2F In conclusion, the duration of ischemia critically determines the importance of MPT on reperfusion injury. Mechanisms other than MPT may play an important role in cell death after less severe ischemia. Content Type Journal ArticleCategory Original ContributionPages 1-10DOI 10.1007/s00395-011-0225-5Authors Marisol Ruiz-Meana, Laboratory of Experimental Cardiology, Vall d’Hebron University Hospital and Research Institute, Universitat Autonoma de Barcelona, Pg. Vall d’Hebron 119-129, 08035 Barcelona, SpainJavier Inserte, Laboratory of Experimental Cardiology, Vall d’Hebron University Hospital and Research Institute, Universitat Autonoma de Barcelona, Pg. Vall d’Hebron 119-129, 08035 Barcelona, SpainCelia Fernandez-Sanz, Laboratory of Experimental Cardiology, Vall d’Hebron Un... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5285369 Fri, 30 Sep 2011 06:29:24 +0100 5285369 http://www.medworm.com/index.php?rid=5285370&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx5804w13m8338688%2F Abstract  TIR-domain-containing adaptor-inducing interferon-β (TRIF) plays a major role in Toll-like receptor 3 (TLR3) mediated signaling. Mice deficient in TLR3 and TRIF have been shown to be highly susceptible to enterovirus-induced myocardial injury. These mice have decreased production of antiviral cytokines and increased viral replication in the heart. Therefore, we hypothesized that conditional overexpression of TRIF would change cardiac myocyte susceptibility to virus infection by augmenting the antiviral response. We generated double-transgenic MHC-tTA/MHCtetO-TRIF mice (DT), with conditional cardiac-specific overexpression of TRIF. Naive DT mice had increased cardiac expression of antiviral cytokines and increased cellular infiltration but no alterations in cardiac... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5285370 Thu, 29 Sep 2011 06:07:44 +0100 5285370 http://www.medworm.com/index.php?rid=5273501&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1158p78x51304356%2F Abstract  Heart failure following acute myocardial infarction (AMI) is a major cause of morbidity and mortality. Our previous observation that injection of apoptotic peripheral blood mononuclear cell (PBMC) suspensions was able to restore long-term cardiac function in a rat AMI model prompted us to study the effect of soluble factors derived from apoptotic PBMC on ventricular remodelling after AMI. Cell culture supernatants derived from irradiated apoptotic peripheral blood mononuclear cells (APOSEC) were collected and injected as a single dose intravenously after myocardial infarction in an experimental AMI rat model and in a porcine closed chest reperfused AMI model. Magnetic resonance imaging (MRI) and echocardiography were used to quantitate cardiac function. Analysis o... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5273501 Wed, 28 Sep 2011 05:48:19 +0100 5273501 http://www.medworm.com/index.php?rid=5208333&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg2w6ju302g72x238%2F We examined whether the presence of ECFCs is associated with preserved microvascular integrity in the myocardium at risk by reducing microvascular obstruction (MVO). We enrolled 88 patients with a first ST elevation AMI. ECFC colonies and circulating progenitor cells were characterized at admission. MVO was evaluated at 5 days and infarct size at 5 days and at 6-month follow-up by magnetic resonance imaging. ECFC colonies were detected in 40 patients (ECFCpos patients). At 5 days, MVO was of greater magnitude in ECFCneg versus ECFCpos patients (7.7 ± 5.3 vs. 3.2 ± 5%, p = 0.0002). At 6 months, in ECFCpos patients, there was a greater reduction in infarct size (−32.4 ± 33 vs. −12.8 ± 24%; p = 0.003) ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5208333 Fri, 09 Sep 2011 05:49:25 +0100 5208333 http://www.medworm.com/index.php?rid=5208334&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5441764552mq2033%2F This study aims to elucidate whether the phenotypic regulation of human vascular smooth muscle cells (VSMC) by estrogen may involve effects on the hyaluronan matrix. VSMC were synchronized by serum withdrawal and subsequently stimulated with 0.001, 0.01, 0.1 and 1 μM estradiol (E2) in the presence or absence of platelet-derived growth factor BB (PDGF-BB) for 24 h. E2 reduced mRNA-expression of hyaluronic acid synthase (HAS) 1 in the presence and absence of PDGF-BB. In contrast, HAS2- and HAS3-mRNA-expression were not affected. This E2-mediated effect on HAS1 mRNA-expression was accompanied by reduced hyaluronan secretion and a shift of HA toward lower molecular weight as evidenced by molecular sieve chromatography. The downregulation of HAS1 was abrogated by the estrogen rec... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5208334 Thu, 08 Sep 2011 06:02:14 +0100 5208334 http://www.medworm.com/index.php?rid=5208335&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flq778hv88g588u01%2F In conclusion, our data suggest that Akt may accentuate aging-induced cardiac geometric and contractile defects through a loss of autophagic regulation. Content Type Journal ArticleCategory Original ContributionPages 1-19DOI 10.1007/s00395-011-0222-8Authors Yinan Hua, Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USAYingmei Zhang, Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USAAsli F. Ceylan-Isik, Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USALoren E. Wold, The Department of Pediatrics, Center for Cardiovascular and Pulmonary Res... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5208335 Thu, 08 Sep 2011 06:02:13 +0100 5208335 http://www.medworm.com/index.php?rid=5208336&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu710p24l3g537133%2F Abstract  Given the established anti-inflammatory properties of mesenchymal stromal cells (MSCs), we investigated their effect on inflammatory cell infiltration of ischemic cardiac tissue and cardiac function. We employed two types of MSCs, human bone marrow-derived (BM) MSCs and human umbilical cord perivascular cells in an experimental acute myocardial infarction (MI) model with the immune-deficient NOD/SCID gamma null mouse. Cells were infused 48 h after induction of MI and mice assessed 24 h later (72 h after MI) for bone marrow (BM), circulating and cardiac tissue-infiltrating monocytes/macrophages. We showed that in the presence of either MSC type, overall macrophage/monocyte levels were reduced, including pro-inflammatory M1-type macrophages, while the ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5208336 Thu, 08 Sep 2011 06:02:12 +0100 5208336 http://www.medworm.com/index.php?rid=5208337&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F28l37746q5616j6p%2F Abstract  K201 has previously been shown to reduce diastolic contractions in vivo during β-adrenergic stimulation and elevated extracellular calcium concentration ([Ca2+]o). The present study characterised the effect of K201 on electrically stimulated and spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca2+ release and contractile events in isolated rat cardiomyocytes during β-adrenergic stimulation and elevated [Ca2+]o. Parallel experiments using confocal microscopy examined spontaneous diastolic Ca2+ release events at an enhanced spatiotemporal resolution. 1.0 μmol/L K201 in the presence of 150 nmol/L isoproterenol (ISO) and 4.75 mmol/L [Ca2+]o significantly decreased the amplitude of diastolic contractions to ~16% of control levels. The stimulat... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5208337 Wed, 07 Sep 2011 15:47:59 +0100 5208337 http://www.medworm.com/index.php?rid=5208338&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx100787913548135%2F Abstract  Heart disease and stroke account for 65% of the deaths in people with diabetes mellitus (DM). DM and hyperglycemia cause systemic inflammation, endothelial dysfunction, a hypercoagulable state with impaired fibrinolysis and increased platelet degranulation, and reduced coronary collateral blood flow. DM also interferes with myocardial protection afforded by preconditioning and postconditioning. Newer anti-diabetic agents should not only reduce serum glucose and HbA1c levels, but also improve cardiovascular outcomes. The older sulfonylurea agent, glyburide, abolishes the benefits of ischemic and pharmacologic preconditioning, but newer sulfonylurea agents, such as glimepiride, may not interfere with preconditioning. GLP-1 analogs and sitagliptin, an oral dipeptidyl... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5208338 Sun, 04 Sep 2011 10:54:26 +0100 5208338 http://www.medworm.com/index.php?rid=5208339&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F63232857jm0271u4%2F Abstract  Eph receptors and ephrin ligands are membrane-bound cell–cell communication molecules with important roles not only in development but also in the physiology of many adult organs. However, their cellular localization and functions in the myocardium are virtually unknown and therefore, we have investigated the expression of EphB receptors and ephrin-B ligands in the rodent heart ventricles and their functions in the rodent cardiomyocytes of primary culture. Examinations by RT-PCR, immunohistochemistry and in situ hybridization revealed that the EphB receptors are preferentially expressed in cardiomyocytes and ephrin-B ligands in the vasculature in adult mouse heart ventricles. Interestingly, we found that inducing high levels of EphB receptor activation in primar... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5208339 Sun, 04 Sep 2011 10:54:25 +0100 5208339 http://www.medworm.com/index.php?rid=5208340&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm652707415610194%2F In this study, we determined whether NF-κB activation within the PVN contributes to sympathoexcitation via interaction with neurotransmitters in the PVN during the pathogenesis of heart failure. Heart failure was induced in rats by left anterior descending coronary artery ligation. Sham-operated control (SHAM) or heart failure rats were treated for 4 weeks through bilateral PVN infusion with SN50, SN50M or vehicle via osmotic minipump. Rats with heart failure treated with PVN vehicle or SN50M (inactive peptide for SN50) had increased levels of glutamate, norepinephrine (NE), tyrosine hydroxylase (TH), superoxide, gp91phox (a subunit of NAD(P)H oxidase), phosphorylated IKKβ and NF-κB p65 activity, and lower levels of gamma-aminobutyric acid (GABA) and the 67-kDa isoform of glut... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5208340 Sun, 04 Sep 2011 10:54:24 +0100 5208340 http://www.medworm.com/index.php?rid=5175614&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm1653162623x5220%2F Abstract  The purpose of this study was to compare the accuracy of post-reperfusion cardiac magnetic resonance (CMR) and pre-reperfusion multidetector computed tomography (MDCT) imaging to measure the size of the area at risk (AAR), using pathology as a reference technique in a porcine acute myocardial infarction model. Fifteen pigs underwent balloon-induced coronary artery occlusion for 40 min followed by reperfusion. The AAR was assessed with arterial enhanced MDCT performed during occlusion, while two different T2 weighted (T2W) CMR imaging sequences and the contrast-enhanced (ce-) CMR endocardial surface length (ESL) were performed after 90 min of reperfusion. Animals were euthanized and the AAR was assessed by pathology. Additional measurements of the myocard... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5175614 Sat, 27 Aug 2011 15:48:16 +0100 5175614 http://www.medworm.com/index.php?rid=5175613&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw714750623741330%2F Abstract  Posttranslational modifications of the transcriptional coactivator PGC-1α by the deacetylase SIRT1 and the kinase AMPK are involved in exercise-induced mitochondrial biogenesis in skeletal muscle. However, similar investigations have not been performed in the left ventricle (LV). Here, we tested whether treadmill training (12 weeks) modifies PGC-1α and mitochondrial biogenesis in gastrocnemius muscle and LV of C57BL/6 J wild-type mice and IL-6-deficient mice with a reported impairment in muscular AMPK activation similarly. Physical activity lowered the plasma insulin and glucose in both mouse strains, suggesting improved insulin sensitivity. The gastrocnemius muscle of IL-6-deficient mice showed reduced mitochondrial respiration and enzyme activity, wh... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5175613 Sat, 27 Aug 2011 15:48:16 +0100 5175613 http://www.medworm.com/index.php?rid=5131915&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy08387562789lvn0%2F Abstract  Local ischemic postconditioning (IPost) and remote ischemic perconditioning (RIPer) are promising methods to decrease ischemia–reperfusion (I/R) injury. We tested whether the use of the two procedures in combination led to an improvement in cardioprotection through a higher activation of survival signaling pathways. Rats exposed to myocardial I/R were allocated to one of the following four groups: Control, no intervention at myocardial reperfusion; IPost, three cycles of 10-s coronary artery occlusion followed by 10-s reperfusion applied at the onset of myocardial reperfusion; RIPer, 10-min limb ischemia followed by 10-min reperfusion initiated 20 min after coronary artery occlusion; IPost+RIPer, IPost and RIPer in combination. Infarct size was significantly... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5131915 Thu, 11 Aug 2011 05:55:41 +0100 5131915 http://www.medworm.com/index.php?rid=5131916&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe74184l6m10l4t24%2F We report that the administration of high-dose atorvastatin to low risk patients undergoing elective CABG surgery, who are already on standard dose ‘statin’ therapy is safe, but does not further reduce perioperative myocardial injury. Content Type Journal ArticlePages 1-9DOI 10.1007/s00395-011-0209-5Authors Andrew J. Ludman, The Hatter Cardiovascular Institute, University College London Hospital, 67 Chenies Mews, London, WC1E 6HX UKDerek J. Hausenloy, The Hatter Cardiovascular Institute, University College London Hospital, 67 Chenies Mews, London, WC1E 6HX UKGirish Babu, The Hatter Cardiovascular Institute, University College London Hospital, 67 Chenies Mews, London, WC1E 6HX UKJonathon Hasleton, The Hatter Cardiovascular Institute, University College London Hospital, 67 Cheni... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5131916 Thu, 11 Aug 2011 05:55:39 +0100 5131916 http://www.medworm.com/index.php?rid=5126182&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj713t84735276k84%2F This study sought to define the role of IFNγ-induced adipose tissue inflammation in endothelial dysfunction in type 2 diabetes. We examined mesenteric adipose tissue (MAT) inflammation, and endothelial function of small mesenteric artery (SMA) in control mice (m Leprdb), diabetic mice (Leprdb), m Leprdb treated with IFNγ, and Leprdb treated with anti-IFNγ or anti-monocyte chemoattractant protein-1 (anti-MCP-1). mRNA and protein expression of IFNγ and MCP-1 were increased in MAT of Leprdb, accompanied by increased T-lymphocyte and macrophage infiltration. Anti-IFNγ reduced MAT inflammatory cell infiltration and inflammatory cytokine expression in Leprdb, while IFNγ treatment showed the opposite effects in m Leprdb. Acetylcholine (ACh)-induced vasorelaxation of SMA was impaired in ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5126182 Mon, 08 Aug 2011 19:55:32 +0100 5126182 http://www.medworm.com/index.php?rid=5109212&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe626619800n08lp0%2F Abstract  Arrhythmias following cardiac stress are a key predictor of death in healthy population. Carbon monoxide (CO) is a ubiquitous pollutant promoting oxidative stress and associated with hospitalization for cardiovascular disease and cardiac mortality. We investigated the effect of chronic CO exposure on the occurrence of arrhythmic events after a cardiac stress test and the possible involvement of related oxidative stress. Wistar rats exposed chronically (4 weeks) to sustained urban CO pollution presented more arrhythmic events than controls during recovery after cardiac challenge with isoprenaline in vivo. Sudden death occurred in 22% of CO-exposed rats versus 0% for controls. Malondialdehyde (MDA), an end-product of lipid peroxidation, was increased in left ve... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5109212 Sat, 06 Aug 2011 05:56:04 +0100 5109212 http://www.medworm.com/index.php?rid=5063523&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ftk63386152623081%2F Abstract  Extensive evidence indicates that heme oxygenase-1 (HO-1) exerts potent cytoprotective effects in response to stress. Previous studies have shown that gene therapy with HO-1 protects against myocardial ischemia/reperfusion injury for up to 8 weeks after gene transfer. However, the long-term effects of HO-1 gene therapy on myocardial ischemic injury and function are unknown. To address this issue, we created a recombinant adeno-associated viral vector carrying the HO-1 gene (rAAV/HO-1) that enables long-lasting transgene expression. Mice received injections in the anterior LV wall of rAAV/LacZ (LacZ group) or rAAV/HO-1 (HO-1 group); 1 year later, they were subjected to a 30-min coronary occlusion (O) and 4 h of reperfusion (R). Cardiac HO-1 gene expre... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5063523 Fri, 22 Jul 2011 17:02:27 +0100 5063523 http://www.medworm.com/index.php?rid=5063525&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx223741614856207%2F Abstract  Excitation–contraction coupling (ECC) in cardiac myocytes involves triggering of Ca2+ release from the sarcoplasmic reticulum (SR) by L-type Ca channels, whose activity is strongly influenced by action potential (AP) profile. The contribution of Ca2+ entry via the Na+/Ca2+ exchanger (NCX) to trigger SR Ca2+ release during ECC in response to an AP remains uncertain. To isolate the contribution of NCX to SR Ca2+ release, independent of effects on SR Ca2+ load, Ca2+ release was determined by recording Ca2+ spikes using confocal microscopy on patch-clamped rat ventricular myocytes with [Ca2+]i fixed at 150 nmol/L. In response to AP clamps, normalized Ca2+ spike amplitudes (ΔF/F 0) increased sigmoidally and doubled as [Na+]i was elevated from 0 to 20 mmol/L wi... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5063525 Thu, 21 Jul 2011 18:07:39 +0100 5063525 http://www.medworm.com/index.php?rid=5063524&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ffw8178t4271r8273%2F Abstract  The ultimate goal of prophylactic gene therapy is to confer permanent protection against ischemia. Although gene therapy with inducible nitric oxide synthase (iNOS) is known to protect against myocardial infarction at 3 days and up to 2 months, the long-term effects on myocardial ischemic injury and function are unknown. To address this issue, we created a recombinant adeno-associated viral vector carrying the iNOS gene (rAAV/iNOS), which enables long-lasting transgene expression. The ability of rAAV/iNOS to direct the expression of functional iNOS protein was confirmed in COS-7 cells before in vivo gene transfer. Mice received injections in the anterior LV wall of rAAV/LacZ or rAAV/iNOS; 1 year later, they underwent a 30-min coronary occlusion (O) a... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5063524 Thu, 21 Jul 2011 18:07:39 +0100 5063524 http://www.medworm.com/index.php?rid=5063526&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe5u32u27q75746m8%2F Abstract  Activation of the atrial renin–angiotensin system plays an important role in the pathophysiology of atrial fibrillation (AF). The pulmonary vein (PV) and left atrium (LA) are important trigger and substrate for the genesis of AF. We investigate the effects of a direct renin inhibitor, aliskiren, on the PV and LA arrhythmogenic activity and the underlying electromechanical mechanisms. Conventional microelectrodes were used to record action potentials and contractility in isolated rabbit PVs and LA tissues before and after the administration of aliskiren (0.1, 1, 3 and 10 μM). By the whole-cell patch clamp and indo-1 fluorimetric ratio techniques, ionic currents and intracellular calcium transient were studied in isolated single PV and LA cardiomyocyte befor... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5063526 Thu, 21 Jul 2011 18:07:38 +0100 5063526 http://www.medworm.com/index.php?rid=5063527&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm4t3265t72258163%2F Abstract  The present study investigates why shedding of the endothelial glycocalyx occurs both in patients undergoing on- and off-pump coronary artery bypass surgery. Release of atrial natriuretic peptide (ANP) was of special interest, because ANP initiates shedding ex vivo. Three major constituents of the glycocalyx (syndecan-1, heparan sulfate and hyaluronan) were measured in arterial blood of patients undergoing coronary artery bypass surgery with (n = 15) and without (n = 15) cardiopulmonary bypass at various phases of the procedure. Additionally, the levels of the inflammatory cytokines interleukin (IL)-6, -8, and -10 and of ANP were evaluated. Elevations of all three components of the glycocalyx were detected in blood of patients undergoing on- (ma... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5063527 Tue, 19 Jul 2011 06:42:10 +0100 5063527 http://www.medworm.com/index.php?rid=5063528&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fdg2520pj04347u7v%2F Abstract  Classically (M1) and alternatively (M2) activated macrophage subsets play differential roles in left ventricular remodeling after myocardial infarction (MI). The precise mechanism underlying the regulation of M1/M2 polarization during MI is unknown. We hypothesized that class A scavenger receptor (SR-A), a key modulator of inflammation, may steer macrophage polarization, which in turn influences cardiomyocytes necrosis after MI. MI was induced in wild type (WT) and SR-A deficient (SR-A−/−) mice by left anterior descending coronary artery ligation. Cardiac function deterioration, ventricular dilatation and fibrosis were all exacerbated in SR-A−/− mice following MI compared to WT littermates. Meanwhile, enhanced M1 macrophage polarization was observed in SR-A�... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5063528 Tue, 19 Jul 2011 06:42:09 +0100 5063528 http://www.medworm.com/index.php?rid=5063529&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv6531n63u7585406%2F Abstract  Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease, which in about 30% of the patients is caused by missense mutations in one allele of the β-myosin heavy chain (β-MHC) gene (MYH7). To address potential molecular mechanisms underlying the family-specific prognosis, we determined the relative expression of mutant versus wild-type MYH7-mRNA. We found a hitherto unknown mutation-dependent unequal expression of mutant to wild-type MYH7-mRNA, which is paralleled by similar unequal expression of β-MHC at the protein level. Relative abundance of mutated versus wild-type MYH7-mRNA was determined by a specific restriction digest approach and by real-time PCR (RT-qPCR). Fourteen samples from M. soleus and myocardium of 12 genotyped and clinically w... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5063529 Tue, 19 Jul 2011 06:42:08 +0100 5063529 http://www.medworm.com/index.php?rid=5030272&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F264184r2r5w278q5%2F This study suggests that coronary microvessels undergo a different pattern of remodeling from macrovessels in type 2 DM. Content Type Journal ArticlePages 1-12DOI 10.1007/s00395-011-0201-0Authors Paige S. Katz, Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, USAAaron J. Trask, Department of Pediatrics, Center for Cardiovascular and Pulmonary Research, The Heart Center, The Research Institute at Nationwide Children’s Hospital, The Ohio State University College of Medicine, 700 Children’s Drive, W303, Columbus, OH 43205, USAFlavia M. Souza-Smith, Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, USAKirk R. Hutchinson, Department of Pediatrics, Center for Cardiovascular and Pulmonary Research... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=5030272 Sun, 10 Jul 2011 05:50:29 +0100 5030272 http://www.medworm.com/index.php?rid=4993639&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9767m163751xv084%2F Abstract  Despite advances in surgical and percutaneous revascularization techniques, nearly one-third of patients with ischemic coronary artery disease are not candidates for revascularization due to suboptimal anatomy or receive suboptimal revascularization from these standard procedures. Neovascularization of the myocardium is not only a physiologic response to ischemia, but also potentially the target of new therapeutic strategies. Induced angiogenesis via protein, gene, and cell-based therapies showed initial promise in experiments using otherwise healthy laboratory animals. However, failure to translate these gains into humans prompted further study into the vascular environment and endothelial dysfunction. Understanding that factors such as hypertension, diabetes, an... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4993639 Wed, 29 Jun 2011 05:58:32 +0100 4993639 http://www.medworm.com/index.php?rid=4977527&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3m25241336237417%2F In this study, we investigated the effects of survivin blockade on burn-induced cardiac apoptosis. Using a standardized Sprague-Dawley rat model of third-degree burn injury over 40% of total body surface area, apoptosis was measured in vivo followed by in vitro assessment of burn serum-stimulated cardiomyocytes. Based on the Western blot analyses, real-time PCR, ELISA, and TUNEL, apoptosis and caspase activation both in vivo and in vitro were significantly increased after severe burn injury, while survivin expression was increased (up to 2.90-fold) during the early stage of burn injury and was almost completely abolished 8 h after the burn. Survivin-deficient cardiomyocytes, as well as hearts from rats treated with the survivin inhibitor YM155, exhibited increased caspase-3 prot... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4977527 Sat, 25 Jun 2011 15:52:04 +0100 4977527 http://www.medworm.com/index.php?rid=4970164&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw3r15vv12428n861%2F Abstract  Therapeutic cell retention and engraftment are critical for myocardial regeneration. Underlying mechanisms, including the role of tissue perfusion, are not well understood. In Wistar Kyoto rats, syngeneic cardiosphere-derived cells (CDCs) were injected intramyocardially, after experimental myocardial infarction. CDCs were labeled with [18F]-FDG (n = 7), for quantification of 1-h retention, or with sodium-iodide-symporter gene (NIS; n = 8), for detection of 24-h engraftment by reporter imaging. Perfusion was imaged simultaneously. Infarct size was 37 ± 9 and 38 ± 9% of LV in FDG and NIS groups. Cell signal was located in the infarct border zone in all animals. No significant relationship was observed between infarct size and ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4970164 Fri, 24 Jun 2011 16:03:43 +0100 4970164 http://www.medworm.com/index.php?rid=4970165&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff237842726v13642%2F Abstract  Circulating microparticles released from various cell types are present in healthy individuals and the number and composition of their membrane vary in different disorders. Long considered to be cellular debris, microparticles have been recently identified as regulatory vectors of intercellular cross-talk. Indeed, circulating microparticles represent a heterogeneous mixture of spheroids of diverse surface membrane glycoproteins and lipids, with diverse cytoplasm components, the pattern of which depends on the type of stimulation and pathophysiology of parental cells. Despite extensive research into the procoagulant and proinflammatory properties of microparticles, there are few data that can provide information on the mechanism(s) of their formation and biological ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4970165 Tue, 21 Jun 2011 20:39:17 +0100 4970165 http://www.medworm.com/index.php?rid=4970166&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn30303325717t8w5%2F Abstract  The in vivo role of TNF signaling in the genesis of β-adrenergic receptor (β-AR)-mediated cardiac hypertrophy is unknown. Wild-type (WT), TNF receptor 1 (TNFR1)-/- and TNFR2-/- mice were given isoproterenol (ISO, 12.5 μg/kg/h) or saline (SAL) for 1 or 7 days. In WT mice, 7 days of ISO yielded chamber/myocyte hypertrophy and hyperdynamic function without hypertension or fibrosis. WT ISO hearts exhibited an early (1 day) pro-inflammatory response with significant (p < 0.05) activation of nuclear factor (NF)-κB and activator protein 1 (AP-1) and upregulation of TNF, interleukin (IL)-1β and IL-6, inducible nitric oxide synthase (iNOS) and monocyte chemotactic protein-1 (MCP-1), together with increased anti-inflammatory IL-10. This ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4970166 Tue, 21 Jun 2011 20:39:16 +0100 4970166 http://www.medworm.com/index.php?rid=4946488&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx11p8q7l294652q7%2F Abstract  In rat atrial myocytes GIRK (Kir3) channels can be activated by acetylcholine and adenosine via M2 and A1 receptors coupled to Pertussis-toxin-sensitive G proteins, such as M2R or A1R. Owing to the lower density of A1R, the amplitude of current activated by a saturating concentration (10 μM) of Ado (IK(Ado)) amounts to about 40% of maximum IK(ACh). Adenovirus-driven overexpression of A1R results in an increase in IK(Ado). In a fraction of A1R-overexpressing cells, both ACh and Ado failed to activate GIRK channels. These cells had a large constitutive Ba2+-sensitive inward rectifying background K+ current, which was insensitive to the GIRK channel inhibitor tertiapin (200 nM), suggesting this current component to be carried by IK1 (Kir) channels. This effect ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4946488 Fri, 17 Jun 2011 11:58:54 +0100 4946488 http://www.medworm.com/index.php?rid=4946489&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe05p334h86q74201%2F Abstract  Mild hypothermia (32–35°C) salvages ischemic myocardium and reduces infarct size in hearts undergoing ischemia/reperfusion. It is clear that a cardioprotective effect is evident when the heart is cooled during ischemia, and the protection is greater as the duration of normothermic ischemia is increasingly limited. The effect of cooling just before and at reperfusion is more controversial. Multiple experimental studies have revealed no effect of mild hypothermia on myocardial infarction when cooling was initiated in the waning minutes of ischemia. But Götberg et al. have demonstrated a small effect in pigs cooled with cold intravenous saline and a venous thermode, although the effect of cooling during ischemia continued to be more prominent. Clinical studies ha... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4946489 Thu, 16 Jun 2011 05:53:19 +0100 4946489 http://www.medworm.com/index.php?rid=4946490&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F98wt008x4381g614%2F Abstract  Two previous clinical trials investigating hypothermia as an adjunct therapy for myocardial infarction have failed. Recently a pilot study has demonstrated a significant reduction in infarct size. The aims of this study were to elucidate the effects of hypothermia on reperfusion injury and to investigate the optimal hypothermia protocol for a future clinical trial. Pigs (40–50 kg) were anesthetized and a normal pig temperature of 38°C was established utilizing an endovascular temperature modulating catheter. The pigs were randomized to a combination hypothermia group (1,000 ml of 4°C saline solution and endovascular cooling, n = 8), or to normothermic controls (n = 8). A PCI balloon was then inflated in the LAD for 40 min (con... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4946490 Wed, 15 Jun 2011 05:53:58 +0100 4946490 http://www.medworm.com/index.php?rid=4903995&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhu64666537q5m9h4%2F Abstract  Necrosis is a type of cell death characterized by a gain in cell volume, swelling of organelles, rupture of the plasma membrane and subsequent loss of intracellular contents. For a long time, the process has been considered as a merely accidental and uncontrolled form of cell death, but accumulating evidence suggests that it can also occur in a regulated fashion. Morphological studies using transmission electron microscopy indicate that the vast majority of dying cells in advanced human atherosclerotic plaques undergo necrosis. Various stimuli in the plaque including high levels of oxidative stress, depletion of cellular ATP, impaired clearance of apoptotic cells and increased intracellular calcium may cause necrotic death. Although the role of necrosis in atheros... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4903995 Wed, 25 May 2011 06:03:37 +0100 4903995 http://www.medworm.com/index.php?rid=4854196&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy1490k12044832q3%2F Abstract  NADPH oxidase family enzymes (or NOXs) are the major sources of reactive oxygen species (ROS) that are implicated in the pathophysiology of many cardiovascular diseases. These enzymes appear to be especially important in the modulation of redox-sensitive signalling pathways that underlie key cellular functions such as growth, differentiation, migration and proliferation. Seven distinct members of the family have been identified of which four (namely NOX1, 2, 4 and 5) may have cardiovascular functions. In this article, we review our current understanding of the roles of NOX enzymes in several common cardiovascular disease states, with a focus on data from genetic studies and clinical data where available. Content Type Journal ArticlePages 1-13DOI 10.1007/s00395... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4854196 Fri, 20 May 2011 05:59:56 +0100 4854196 http://www.medworm.com/index.php?rid=4831080&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe5570w0p8l003967%2F In conclusion, EPC phenotype, genotype and function were differentially affected by mCRP and pCRP, strongly arguing for differential roles of these two CRP conformations. The up-regulation of interferon-inducible genes in response to mCRP may constitute a mechanism for the local regulation of EPC function. Content Type Journal ArticlePages 1-17DOI 10.1007/s00395-011-0191-yAuthors I. Ahrens, Department of Cardiology and Angiology, University Hospital Freiburg, Hugstetter Street 55, 79106 Freiburg, GermanyH. Domeij, Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, Melbourne, AustraliaS. U. Eisenhardt, Department of Plastic and Hand Surgery, University Hospital Freiburg, Freiburg, GermanyD. Topcic, Atherothrombosis and Vascular Biology, Baker IDI Heart a... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4831080 Thu, 12 May 2011 18:54:30 +0100 4831080 http://www.medworm.com/index.php?rid=4821803&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7363739646858m21%2F Content Type Journal ArticlePages 1-5DOI 10.1007/s00395-011-0188-6Authors Henning Morawietz, Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University of Technology Dresden, Fetscherstr. 74, 01307 Dresden, Germany Journal Basic Research in CardiologyOnline ISSN 1435-1803Print ISSN 0300-8428 (Source: Basic Research in Cardiology) Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4821803 Wed, 11 May 2011 06:25:53 +0100 4821803 http://www.medworm.com/index.php?rid=4821804&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm76611962875866u%2F Abstract  The role of glycogen synthase kinase 3 beta (GSK-3β) in modulating Notch control of vascular smooth muscle cell (vSMC) growth (proliferation and apoptosis) was examined in vitro under varying conditions of cyclic strain and validated in vivo following changes in medial tension and stress. Modulation of GSK-3β in vSMC following ectopic expression of constitutively active GSK-3β, siRNA knockdown and pharmacological inhibition with SB-216763 demonstrated that GSK-3β positively regulates Notch intracellular domain expression, CBF-1/RBP-Jκ transactivation and downstream target gene mRNA levels, while concomitantly promoting vSMC proliferation and inhibiting apoptosis. In contrast, inhibition of GSK-3β attenuated Notch signaling and decreased vSMC proliferation an... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4821804 Tue, 10 May 2011 05:56:11 +0100 4821804 http://www.medworm.com/index.php?rid=4805753&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr31557982t567513%2F Abstract  Perioperative myocardial ischemia contributes to postoperative morbidity and mortality. Remote intermittent ischemia (RI) has been shown to benefit patients undergoing coronary artery bypass graft (CABG) surgery by decreasing postoperative cardiac troponin levels. In addition, there is evidence that volatile anesthetics may provide myocardial protection. In this prospective randomized controlled trial we tested the hypothesis that RI is cardioprotective under a strict anesthetic regime with volatile anesthesia until cardiopulmonary bypass (CPB). We also assessed whether RI modulates postoperative cytokine and growth factor concentrations. Fifty-four patients referred for elective CABG surgery without concomitant valve or aortic surgery were randomized to three 5-m... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4805753 Thu, 05 May 2011 05:45:16 +0100 4805753 http://www.medworm.com/index.php?rid=4805754&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9g7442k571743533%2F In conclusion, the present data show that Hif-1α regulation is essential for survival of oxLDL-treated macrophages independent of the oxygen tension. Therefore, this newly characterized mechanism might also have an important influence for the vulnerability of atherosclerotic plaques. Content Type Journal ArticlePages 1-12DOI 10.1007/s00395-011-0186-8Authors David M. Poitz, Department of Internal Medicine and Cardiology, University of Technology Dresden, Fetscherstr. 74, 01307 Dresden, GermanyAntje Augstein, Department of Internal Medicine and Cardiology, University of Technology Dresden, Fetscherstr. 74, 01307 Dresden, GermanySönke Weinert, Department of Internal Medicine and Cardiology, University of Technology Dresden, Fetscherstr. 74, 01307 Dresden, GermanyRüdiger C. Braun-... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4805754 Thu, 05 May 2011 05:45:14 +0100 4805754 http://www.medworm.com/index.php?rid=4805755&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg757285843275821%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s00395-011-0187-7Authors Jürgen Peters, Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen, Universitätsklinikum Essen, Hufelandstr. 55, 4511 Essen, Germany Journal Basic Research in CardiologyOnline ISSN 1435-1803Print ISSN 0300-8428 (Source: Basic Research in Cardiology) Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4805755 Thu, 05 May 2011 05:45:13 +0100 4805755 http://www.medworm.com/index.php?rid=4805756&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh021w84728355n8l%2F Abstract  Hematopoietic cytokines, traditionally known to influence cellular proliferation, differentiation, maturation, and lineage commitment in the bone marrow, include granulocyte colony-stimulating factor (G-CSF), granulocyte–macrophage colony-stimulating factor, stem cell factor, Flt-3 ligand, and erythropoietin among others. Emerging evidence suggests that these cytokines also exert multifarious biological effects on diverse nonhematopoietic organs and tissues. Although the precise mechanisms remain unclear, numerous studies in animal models of myocardial infarction (MI) and heart failure indicate that hematopoietic cytokines confer potent cardiovascular benefits, possibly through mobilization and subsequent homing of bone marrow-derived cells into the infarcted he... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4805756 Wed, 04 May 2011 05:45:12 +0100 4805756 http://www.medworm.com/index.php?rid=4782303&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F285510r04h2861w7%2F Abstract  Chronic pressure-overload and diabetes mellitus are two frequent disorders affecting the heart. We aimed to characterize myocardial structural and functional changes induced by both conditions. Pressure-overload was established in Wistar-han male rats by supra-renal aortic banding. Six-weeks later, diabetes was induced by streptozotocin (65 mg/kg,ip), resulting in four groups: SHAM, banding (BA), diabetic (DM) and diabetic-banding (DB). Six-weeks later, pressure–volume loops were obtained and left ventricular samples were collected to evaluate alterations in insulin signalling pathways, extracellular matrix as well as myofilament function and phosphorylation. Pressure-overload increased cardiomyocyte diameter (BA 22.0 ± 0.4 μm, SHAM 18.2&nbs... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4782303 Sat, 30 Apr 2011 23:40:46 +0100 4782303 http://www.medworm.com/index.php?rid=4782304&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh1p7317022095647%2F Abstract  Activation of NF-κB contributes to cardiac hypertrophy and the interleukin-1 receptor (IL-1R)-mediated MyD88-dependent signaling pathway predominately activates NF-κB. Recent studies have shown that the TIR/BB-Loop mimetic (AS-1) disrupted the interaction of MyD88 with the IL-1R, resulting in blunting of NF-κB activation. We have examined the effects of AS-1 on the IL-1β-induced hypertrophic response using cultured neonatal cardiac myocytes in vitro and transverse aortic constriction (TAC) pressure overload-induced cardiac hypertrophy in vivo. Neonatal cardiac myocytes were treated with AS-1 15 min prior to IL-1β stimulation for 24 h. AS-1 treatment significantly attenuated IL-1β-induced hypertrophic responses of cardiac myocytes. In vivo experiment... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4782304 Sat, 30 Apr 2011 23:40:45 +0100 4782304 http://www.medworm.com/index.php?rid=4782305&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg1237012612u4732%2F Abstract  NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are known to be involved in angiotensin II-induced hypertension and endothelial dysfunction. Several Nox isoforms are expressed in the vessel wall, among which Nox2 is especially abundant in the endothelium. Endothelial Nox2 levels rise during hypertension but little is known about the cell-specific role of endothelial Nox2 in vivo. To address this question, we generated transgenic mice with endothelial-specific overexpression of Nox2 (Tg) and studied the effects on endothelial function and blood pressure. Tg had an about twofold increase in endothelial Nox2 levels which was accompanied by an increase in p22phox levels but no change in levels of other Nox isoforms or endothelial nitric oxide synthase (eNOS)... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4782305 Fri, 29 Apr 2011 05:43:19 +0100 4782305 http://www.medworm.com/index.php?rid=4771853&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg2876l60061u27w5%2F Abstract  A model of intracoronary stem cell delivery that enables transgenesis/gene targeting would be a powerful tool but is still lacking. To address this gap, we compared intracoronary and intramyocardial delivery of lin−/c-kit+/GFP+ cardiac stem cells (CSCs) in a murine model of reperfused myocardial infarction (MI). Lin−/c-kit+/GFP+ CSCs were successfully expanded from GFP transgenic hearts and cultured with no detectable phenotypic change for up to ten passages. Intracoronary delivery of CSCs 2 days post-MI resulted in significant alleviation of adverse LV remodeling and dysfunction, which was at least equivalent, if not superior, to that achieved with intramyocardial delivery. Compared with intramyocardial injection, intracoronary infusion was associated with... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4771853 Sun, 24 Apr 2011 05:32:22 +0100 4771853 http://www.medworm.com/index.php?rid=4754901&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F363g3l640136546k%2F In this study, we show that TGFβ-induced EMT is dependent on type-1 TGFβ receptor activity and can be inhibited by soluble VCAM-1. We also show that epicardial-specific knockdown of Wilms tumor-1 (WT1) induces the process of EMT in human adult epicardial cells, through transcriptional regulation of platelet-derived growth factor receptor alpha (Pdgfrα), Snai1 and VCAM-1. These data provide new insights into the process of EMT in human adult epicardial cells, which might provide opportunities to develop new strategies for endogenous cell-based cardiac repair. Content Type Journal ArticlePages 1-19DOI 10.1007/s00395-011-0181-0Authors Noortje A. M. Bax, Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The NetherlandsAngelique A. M. van Oorschot, De... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4754901 Sat, 23 Apr 2011 15:41:13 +0100 4754901 http://www.medworm.com/index.php?rid=4725495&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq01km020281721x8%2F In conclusion, these data demonstrate the importance of MnSOD and KLF4 for proliferation control in VSMC. Our results provide novel insights into how proliferation of VSMC is regulated by estrogen and may help to identify novel targets for the treatment of vascular diseases such as restenosis. Content Type Journal ArticlePages 1-13DOI 10.1007/s00395-011-0174-zAuthors Derya Sivritas, Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, GermanyMarc Ulrich Becher, Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, GermanyTalin Ebrahimian, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montréal, QC, CanadaOmar Arfa, Lady Davis Institute for Medic... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4725495 Tue, 12 Apr 2011 06:55:10 +0100 4725495 http://www.medworm.com/index.php?rid=4710147&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3154v3160778621x%2F This study demonstrated that the ROS-induced formation of a positive-feedback loop ROS–p38 MAPK–mtCx43 for the sustained activation of p38 MAPK soon after birth possibly contributes to the loss of cell division and binucleation in mammalian cardiomyocytes. Content Type Journal ArticlePages 1-14DOI 10.1007/s00395-011-0178-8Authors Daisuke Matsuyama, Laboratory of Cellular Cybernetics, Graduate School of Information Science and Technology, Hokkaido University, Sapporo, 060-0814 JapanKoichi Kawahara, Laboratory of Cellular Cybernetics, Graduate School of Information Science and Technology, Hokkaido University, Sapporo, 060-0814 Japan Journal Basic Research in CardiologyOnline ISSN 1435-1803Print ISSN 0300-8428 (Source: Basic Research in Cardiology) Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4710147 Fri, 08 Apr 2011 16:58:55 +0100 4710147 http://www.medworm.com/index.php?rid=4698213&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft7k962x21107q747%2F Abstract  Implantation of bare metal stents (BMS) induces the release not only of particulate debris, but also of soluble vasoconstrictors which contribute to microvascular impairment. So this study aimed at addressing the potential attenuation of such vasoconstriction using paclitaxel eluting stents (PES). Using a distal protection/aspiration device, coronary arterial blood was retrieved before and during stent [n = 14 BMS, n = 14 PES, n = 3 sirolimus eluting stents (SES)] implantation in patients with saphenous vein aorto-coronary bypass stenosis and analyzed for plasma serotonin and thromboxane B2 concentrations. The vasoconstriction of rat mesenteric arteries with intact (+E) and denuded (−E) endothelium in response to coronary arterial or... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4698213 Wed, 06 Apr 2011 16:29:01 +0100 4698213 http://www.medworm.com/index.php?rid=4693755&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk242j795361xj66m%2F In this study, we showed that preconditioning with sulfur dioxide 10 min before ischemia (with a low concentration of sulfur dioxide of 1–10 μmol/kg) could reduce myocardial infarct size and plasma activities of lactate dehydrogenase and creatine kinase in rats with I/R in vivo. Sulfur dioxide preconditioning also reduced myocardium apoptosis induced by I/R. In addition, sulfur dioxide preconditioning increased cardiac function in vitro. Sulfur dioxide preconditioning induced expression of myocardial glucose-regulated protein 78 (GRP78) and phosphorylated eukaryotic initiation of the factor 2α-subunit (p-eIF2α) prior to myocardial I/R but suppressed expression of myocardial GRP78, C/EBP homologous protein, and p-eIF2α during myocardial I/R, in association with improve... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4693755 Wed, 06 Apr 2011 06:45:22 +0100 4693755 http://www.medworm.com/index.php?rid=4686153&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2648584258884r51%2F Abstract  Desmosomes are cell–cell adhesion sites and part of the intercalated discs, which couple adjacent cardiomyocytes. The connection is formed by the extracellular domains of desmosomal cadherins that are also linked to the cytoskeleton on the cytoplasmic side. To examine the contribution of the desmosomal cadherin desmoglein 2 to cardiomyocyte adhesion and cardiac function, mutant mice were prepared lacking a part of the extracellular adhesive domain of desmoglein 2. Most live born mutant mice presented normal overall cardiac morphology at 2 weeks. Some animals, however, displayed extensive fibrotic lesions. Later on, mutants developed ventricular dilation leading to cardiac insufficiency and eventually premature death. Upon histological examination, cardiomyo... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4686153 Thu, 31 Mar 2011 17:40:26 +0100 4686153 http://www.medworm.com/index.php?rid=4632273&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv0g1557577n3321w%2F Abstract  Stem cells possessing the potential to replace damaged myocardium with functional myocytes have drawn increasing attention in the past decade in treating ischemic heart diseases; these diseases are the leading cause of morbidity and mortality in the world. The adult heart has recently been shown to contain a few cardiac stem cells (CSCs) that, in theory, suggest cardiac repair following acute myocardial infarction is possible if the CSC titer could be increased. Stem cell-based therapies, including hematopoietic stem cells and mesenchymal stem cells, were proven to be marginal and transitional. Multiple factors and mechanisms, rather than direct cardiac regeneration are involved in stem cell-mediated cardiac functional improvement. This review will focus on (1) th... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4632273 Tue, 22 Mar 2011 06:07:11 +0100 4632273 http://www.medworm.com/index.php?rid=4623137&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flr111n883h2uw160%2F Abstract  Current available biomarkers cannot identify myocardial ischemia without necrosis. To overcome this issue and to increase diagnostic power, we evaluated the activation of the three MAPK pathways, ERK1/2, JNK and p38, in T lymphocytes of patients with acute coronary syndromes (ACS). We included sixty consecutive patients affected by either unstable angina (UA, N = 22), Non- ST-segment elevation MI (NSTEMI, N = 19) or ST-segment elevation MI (STEMI, N = 19). Two separate groups of patients were matched as controls: healthy subjects (CTRL, N = 20) and patients with stable coronary artery disease (CAD, N = 21). MAPK activation in T lymphocytes, measured by phospho-ERK1/2, phospho-JNK and phospho-p38 levels, was assessed by... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4623137 Sun, 20 Mar 2011 05:33:40 +0100 4623137 http://www.medworm.com/index.php?rid=4616506&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fgh33281583585178%2F Abstract  Heat shock proteins (HSPs) are among the most highly conserved and immunogenic proteins shared by microbial agents and mammals. Human (h) HSP60 is upregulated under stress conditions and serves as a target for cross-reactive cytotoxic HSP-serum-antibodies. The present study evaluates the expressions of hHSP60 and its homologue chlamydial (c) HSP60 in advanced human coronary lesions and correlates intimal tissue-bound HSP expressions with circulating HSP-antibodies. Coronary atherectomy specimens retrieved from 100 primary target lesions of patients with unstable angina (UA; n = 40) or stable angina (SA; n = 60) were assessed immunohistochemically for the presence of hHSP60 and cHSP60. In a subgroup (n = 40), blood samples were tested fo... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4616506 Fri, 18 Mar 2011 01:56:01 +0100 4616506 http://www.medworm.com/index.php?rid=4616507&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F963476771l7523l2%2F Abstract  Congestive heart failure developing after acute myocardial infarction (AMI) is a major cause of morbidity and mortality. Clinical trials of cell-based therapy after AMI evidenced only a moderate benefit. We could show previously that suspensions of apoptotic peripheral blood mononuclear cells (PBMC) are able to reduce myocardial damage in a rat model of AMI. Here we experimentally examined the biochemical mechanisms involved in preventing ventricular remodelling and preserving cardiac function after AMI. Cell suspensions of apoptotic cells were injected intravenously or intramyocardially after experimental AMI induced by coronary artery ligation in rats. Administration of cell culture medium or viable PBMC served as controls. Immunohistological analysis was perfor... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4616507 Thu, 17 Mar 2011 18:32:03 +0100 4616507 http://www.medworm.com/index.php?rid=4594131&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F81758h75412n1770%2F Abstract  Cooling the ischemic heart by just a few degrees protects it from infarction without affecting its mechanical function, but the mechanism of this protection is unknown. We investigated whether signal transduction pathways might be involved in the anti-infarct effect of mild hypothermia (35°C). Isolated rabbit hearts underwent 30 min of coronary artery occlusion/2 h of reperfusion. They were either maintained at 38.5°C or cooled to 35°C just before and only during ischemia. Infarct size was measured. The effects of the protein kinase C inhibitor chelerythrine, the nitric oxide synthase inhibitor N ω-nitro-l-arginine methyl ester (l-NAME), the phosphatidylinositol 3-kinase antagonist wortmannin, or either of the mitogen-activated protein kinase kinase ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4594131 Sat, 12 Mar 2011 07:00:54 +0100 4594131 http://www.medworm.com/index.php?rid=4581746&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm426q1363810mm12%2F In conclusion, an ARE-like/Oct-1 binding site was noticed to be essential for shear stress-dependent downregulation of Nox4. This novel mechanism may be involved in the flow-dependent downregulation of endothelial superoxide anion formation. Content Type Journal ArticlePages 1-11DOI 10.1007/s00395-011-0170-3Authors Claudia Goettsch, Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University of Technology Dresden, Fetscherstr. 74, 01307 Dresden, GermanyWinfried Goettsch, Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University of Technology Dresden, Fetscherstr. 74, 01307 Dresden, GermanyMelanie Brux, Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University of Technology Dre... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4581746 Fri, 11 Mar 2011 18:09:57 +0100 4581746 http://www.medworm.com/index.php?rid=4581747&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy50267345671j321%2F Abstract  Nitric oxide (NO)-dependent soluble guanylate cyclase (sGC) activation is an important component of cardiac signal transduction pathways, including the cardioprotective signaling cascade induced by ischemic preconditioning (IPC). The sGCα subunit, which binds to the common sGCβ1 subunit, exists in two different isoforms, sGCα1 and sGCα2, but their relative physiological roles remain unknown. In the present study, we studied Langendorff-perfused isolated hearts of genetically engineered mice lacking functional sGCα1 (sGCα1KO mice), which is the predominant isoform in the heart. Our results show that the loss of sGCα1 has a positive inotropic and lusitropic effect on basal cardiac function, indicating an important role for sGCα1 in regulating basal myocardia... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4581747 Fri, 11 Mar 2011 06:51:23 +0100 4581747 http://www.medworm.com/index.php?rid=4578465&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy670317n4108x6q4%2F Abstract  Increased activity of the sympathetic system is an important feature contributing to the pathogenesis and progression of chronic heart failure. While the mechanisms and consequences of enhanced norepinephrine release from sympathetic nerves have been intensely studied, the role of the adrenal gland in the development of cardiac hypertrophy and progression of heart failure is less well known. Thus, the aim of the present study was to determine the effect of chronic cardiac pressure overload in mice on adrenal medulla structure and function. Cardiac hypertrophy was induced in wild-type mice by transverse aortic constriction (TAC) for 8 weeks. After TAC, the degree of cardiac hypertrophy correlated significantly with adrenal weight and adrenal catecholamine stor... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4578465 Thu, 10 Mar 2011 06:55:24 +0100 4578465 http://www.medworm.com/index.php?rid=4578466&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fft60533484v2875h%2F Content Type Journal ArticlePages 1-4DOI 10.1007/s00395-011-0169-9Authors Karin Przyklenk, Cardiovascular Research Institute, Wayne State University School of Medicine, Elliman Building, Room 1107, 421 E Canfield, Detroit, MI 48201, USAPeter Whittaker, Cardiovascular Research Institute, Wayne State University School of Medicine, Elliman Building, Room 1107, 421 E Canfield, Detroit, MI 48201, USA Journal Basic Research in CardiologyOnline ISSN 1435-1803Print ISSN 0300-8428 (Source: Basic Research in Cardiology) Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4578466 Thu, 10 Mar 2011 06:55:23 +0100 4578466 http://www.medworm.com/index.php?rid=4578467&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl7r28650k7128486%2F In this study, we examined the effect of Hsp70 deletion on AIF-induced apoptosis during ischemia/reperfusion (I/R) in vivo. Although Hsp70 KO and WT mice demonstrated similar amounts of AIF released from mitochondria after I/R surgery, Hsp70 KO mice showed a significantly greater increase in apoptosis, larger infarct size, and decreased cardiac output. There was also a significant fourfold increase in the nuclear accumulation of AIF in Hsp70 KO mice compared with WT mice. Treatment with 4-AN (4-amino-1,8-napthalimide, 3 mg/kg), a potent inhibitor of PARP-1, which is a critical regulator of AIF-induced apoptosis, significantly blocked the release of AIF from mitochondria and the translocation of AIF into the nuclei after I/R in both WT and Hsp70 KO mice. In addition, 4-AN treatme... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4578467 Wed, 09 Mar 2011 06:57:17 +0100 4578467 http://www.medworm.com/index.php?rid=4561591&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv51287nhv3v19032%2F In this study, we hypothesized that EGFR trans-activation by UTII might exert a protective effect in the overloaded heart. To test this hypothesis, we induced cardiac hypertrophy by transverse aortic constriction (TAC) in wild-type mice, and tested the effects of the UTII antagonist Urantide (UR) on cardiac function, structure, and EGFR trans-activation. After 7 days of pressure overload, UR treatment induced a rapid and significant impairment of cardiac function compared to vehicle. In UR-treated TAC mice, cardiac dysfunction was associated with reduced phosphorylation levels of the EGFR and extracellular-regulated kinase (ERK), increased apoptotic cell death and fibrosis. In vitro UTR stimulation induced membrane translocation of β-arrestin 1/2, EGFR phosphorylation/internali... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4561591 Thu, 03 Mar 2011 08:48:21 +0100 4561591 http://www.medworm.com/index.php?rid=4541358&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fth14g2nl83128t2q%2F Abstract  Pioglitazone (PIO), a PPAR-γ agonist, limits myocardial infarct size by activating Akt and upregulating cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX)-2. However, PIO has several PPAR-γ-independent effects. We assessed whether PIO limits myocardial infarct size in PPAR-γ–knockout mice, attenuates hypoxia-reoxygenation injury and upregulates P-Akt, cPLA2, and COX-2 expression in PPAR-γ–knockout cardiomyocytes. Cardiac-specific inducible PPAR-γ knockout mice were generated by crossing αMHC-Cre mice to PPAR-γloxp/loxp mice. PPAR-γ deletion was achieved after 7 days of intraperitoneal tamoxifen (20 mg/kg/day) administration. Mice received PIO (10 mg/kg/day), or vehicle, for 3 days and underwent coronary occlusion (30 min... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4541358 Mon, 28 Feb 2011 16:44:32 +0100 4541358 http://www.medworm.com/index.php?rid=4541359&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F32737253rr568353%2F In this study, we examined the comparative effects of elevation of wild type and activated NHE1. Two mouse transgenic models that expressed either a wild type NHE1 protein or an activated NHE1 protein were characterized. Expression of activated NHE1 caused significant increases in heart weight to body weight, apoptosis, cross-sectional area, interstitial fibrosis and decreased cardiac performance. Expression of wild type NHE1 caused a much milder pathology. When we examined 2 or 10-week-old mouse hearts, there was neither elevation of calcineurin levels nor increased phosphorylation of ERK or p38 in either NHE1 transgenic mouse line. Expression of activated NHE1 in intact mice caused an increased sensitivity to phenylephrine-induced hypertrophy. Our results show that expression of ac... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4541359 Sat, 26 Feb 2011 21:43:22 +0100 4541359 http://www.medworm.com/index.php?rid=4541360&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F52772x60x1v4h9kg%2F Abstract  Increasing evidence indicates that high levels of serum erythropoietin (Epo) can lessen ischemia–reperfusion injury in the heart and multiple cardiac cell types have been suggested to play a role in this Epo effect. To clarify the mechanisms underlying this cardioprotection, we explored Epo treatment of coronary artery endothelial cells and Epo cardioprotection in a Mus musculus model with Epo receptor expression restricted to hematopoietic and endothelial cells (ΔEpoR). Epo stimulation of coronary artery endothelial cells upregulated endothelial nitric oxide synthase (eNOS) activity in vitro and in vivo, and enhanced nitric oxide (NO) production that was determined directly by real-time measurements of gaseous NO release. Epo stimulated phosphoinositide 3-kina... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4541360 Wed, 23 Feb 2011 23:33:03 +0100 4541360 http://www.medworm.com/index.php?rid=4484118&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2520021948075712%2F In conclusion, HTEA inhibited electrical and nerve remodeling and reduced the maintenance of AF in a canine AF model, in which process HTEA exhibited anti-inflammatory and antioxidant effects, indicating that, in addition to the efferent cardiac sympathetic nerve, afferent fibers also play an important role in the initiation and/or maintenance of AF. Content Type Journal ArticlePages 1-12DOI 10.1007/s00395-011-0154-3Authors Shu-sen Yang, Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001 People’s Republic of ChinaWei Han, Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001 People’s Republic of ChinaYong ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4484118 Mon, 14 Feb 2011 06:55:20 +0100 4484118 http://www.medworm.com/index.php?rid=4484119&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh635481511238465%2F Abstract  Elevated levels of cardiac mitochondrial uncoupling protein 3 (UCP3) and decreased cardiac efficiency (hydraulic power/oxygen consumption) with abnormal cardiac function occur in obese, diabetic mice. To determine whether cardiac mitochondrial uncoupling occurs in non-genetic obesity, we fed rats a high fat diet (55% kcal from fat) or standard laboratory chow (7% kcal from fat) for 3 weeks, after which we measured cardiac function in vivo using cine MRI, efficiency in isolated working hearts and respiration rates and ADP/O ratios in isolated interfibrillar mitochondria; also, measured were medium chain acyl-CoA dehydrogenase (MCAD) and citrate synthase activities plus uncoupling protein 3 (UCP3), mitochondrial thioesterase 1 (MTE-1), adenine nucleotide transl... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4484119 Fri, 11 Feb 2011 11:50:25 +0100 4484119 http://www.medworm.com/index.php?rid=4471115&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F46u288rx5146p627%2F In this study, we sought to determine the role of a newly identified E3 ligase, neuregulin receptor degradation protein-1 (Nrdp1), on cardiac ischemia/reperfusion (I/R) injury. I/R injury markedly upregulated Nrdp1 expression in heart tissue. To elucidate the role of Nrdp1 in I/R-induced cardiac injury, neonatal cardiomyocytes were infected with adenoviral constructs expressing wild-type, dominant-negative Nrdp1 genes. Increased Nrdp1 expression enhanced I/R-induced cardiomyocyte apoptosis and inflammation as compared with the green fluorescent protein (GFP) control; these effects were attenuated by overexpression of a dominant-negative Nrdp1 (C34S/H36Q). Furthermore, cardiac-specific Nrdp1 overexpression in vivo in mouse significantly increased infarct size, the number of TUNEL-posi... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4471115 Thu, 10 Feb 2011 19:55:54 +0100 4471115 http://www.medworm.com/index.php?rid=4451252&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9228758148588x18%2F Abstract  Intermittent hypobaric hypoxia (IHH) preconditioning protects the heart against ischemic injuries. However, little is known about the therapeutic effect of IHH on myocardial infarction (MI). The aim of this study was to test whether IHH treatment influences infarct size and cardiac performance after MI. Seven days after sham operation or left anterior descending coronary artery ligation, male Sprague–Dawley rats were randomly exposed to normoxia or one 6-h period each day of IHH (5,000 m) for 14 and 28 days. Echocardiography analysis showed that IHH significantly reduced left ventricular (LV) dilation and improved cardiac performance after 14- or 28-day treatment compared with MI-normoxic groups. The improvement of LV function was further confirmed in ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4451252 Sun, 06 Feb 2011 16:31:23 +0100 4451252 http://www.medworm.com/index.php?rid=4451253&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0qh626tp06681h12%2F Abstract  In isolated cells, soluble guanylyl cyclase (sGC) activity is regulated by exogenous nitric oxide (NO) via downregulation of expression and posttranslational S-nitrosylation. The aim of this study was to investigate whether such regulatory mechanism impact on endothelium-dependent vasodilation in a newly developed mouse strain carrying an endothelial-specific overexpression of eNOS (eNOS++). When compared with transgene negative controls (eNOSn), eNOS++-mice showed a 3.3-fold higher endothelial-specific aortic eNOS expression, increased vascular cGMP and VASP phosphorylation, a L-nitroarginine (L-NA)-inhibitable decrease in systolic blood pressure, but normal levels of peroxynitrite and nitrotyrosine formation, endothelium-dependent aortic vasodilation and vasodilat... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4451253 Sun, 06 Feb 2011 06:39:07 +0100 4451253 http://www.medworm.com/index.php?rid=4442705&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj75j0h1855506528%2F In conclusion, clopidogrel improved endothelial function and NO bioavailability in heart failure. During CHF, sensitivity to P2Y12 signaling was increased leading to impaired adenylyl cyclase-mediated signaling. Chronic P2Y12-blockade with clopidogrel improved adenylyl cyclase-mediated signaling including increased AKT- and eNOS-phosphorylation contributing to improved NO-mediated vasorelaxation. Content Type Journal ArticlePages 1-10DOI 10.1007/s00395-011-0153-4Authors Andreas Schäfer, Klinik für Kardiologie und Angiologie, Zentrum Innere Medizin, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, GermanyDaniela Fraccarollo, Klinik für Kardiologie und Angiologie, Zentrum Innere Medizin, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4442705 Thu, 03 Feb 2011 07:14:39 +0100 4442705 http://www.medworm.com/index.php?rid=4442706&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh598u48325102533%2F In this study, we explored the hypothesis that CRH in the PVN contributes to sympathoexcitation via interaction with neurotransmitters in heart failure (HF). Sprague–Dawley rats with HF or sham-operated controls (SHAM) were treated for 4 weeks with a continuous bilateral PVN infusion of the selective CRH-R1 antagonist NBI-27914 or vehicle. Rats with HF had higher levels of glutamate, norepinephrine (NE) and tyrosine hydroxylase (TH), and lower levels of gamma-aminobutyric acid (GABA) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN when compared to SHAM rats. Plasma levels of cytokines, NE, ACTH and renal sympathetic nerve activity (RSNA) were increased in HF rats. Bilateral PVN infusions of NBI-27914 attenuated the decreases in PVN GABA and GAD67, and the... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4442706 Thu, 03 Feb 2011 07:14:38 +0100 4442706 http://www.medworm.com/index.php?rid=4429682&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F93845183013p7644%2F Abstract  Activation of the Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway is known to play a key role in cardiogenesis and to afford cardioprotection against ischemia–reperfusion in adult. However, involvement of JAK2/STAT3 pathway and its interaction with other signaling pathways in developing heart transiently submitted to anoxia remains to be explored. Hearts isolated from 4-day-old chick embryos were submitted to anoxia (30 min) and reoxygenation (80 min) with or without the antioxidant MPG, the JAK2/STAT3 inhibitor AG490 or the PhosphoInositide-3-Kinase (PI3K)/Akt inhibitor LY-294002. Time course of phosphorylation of STAT3αtyrosine705 and Reperfusion Injury Salvage Kinase (RISK) proteins [PI3K, Akt, Glycogen Synthas... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4429682 Sat, 29 Jan 2011 06:49:04 +0100 4429682 http://www.medworm.com/index.php?rid=4400804&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe358086435605341%2F In this study, we developed a statistically rigorous method to uniquely quantify various I Kv in adult mouse ventricular myocytes, and concluded that tri-exponential functions combined with depolarizing pulses of duration greater than 20 s are essential to adequately separate the different I Kv components. This method enabled us to reliably dissect the kinetic components of the decay phase of I Kv into fast (I to), intermediate (KV1.5-encoded I K,slow1) and slow (KV2-encoded I K,slow2) components. The most rapid kinetic phase, I to, can be further dissected into fast (KV4-encoded I to,f) and slow (KV1.4-encoded I to,s) components by measuring recovery from inactivation, voltage-dependence of activation and sensitivity to HpTx-2 and 4-AP. The applicability of our dissection... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4400804 Fri, 21 Jan 2011 15:07:47 +0100 4400804 http://www.medworm.com/index.php?rid=4383392&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F28119772v5442157%2F Abstract  Protection achieved by ischemic preconditioning is dependent on A2B adenosine receptors (A2BAR) in rabbit and mouse hearts and, predictably, an A2BAR agonist protects them. But it is controversial whether cardiomyocytes themselves actually express A2BAR. The present study tested whether A2BAR could be demonstrated on rat cardiomyocytes. Isolated rat hearts experienced 30 min of ischemia and 120 min of reperfusion. The highly selective, cell-permeant A2BAR agonist BAY60-6583 (500 nM) infused at reperfusion reduced infarct size from 40.4 ± 2.0% of the risk zone in control hearts to 19.9 ± 2.8% indicating that A2BAR are protective in rat heart as well. Furthermore, BAY60-6583 reduced calcium-induced mitochondrial permeability transiti... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4383392 Wed, 19 Jan 2011 09:30:05 +0100 4383392 http://www.medworm.com/index.php?rid=4383394&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F137721345551r476%2F This study examined the effect of central tumor necrosis factor-alpha (TNF) blockade on the imbalance between nitric oxide and superoxide production in the paraventricular nucleus (PVN) and ventrolateral medulla (VLM), key autonomic regulators, and their contribution to enhanced sympathetic drive in mice with congestive heart failure (CHF). We also used a TNF gene knockout (KO) mouse model to study the involvement of TNF in body fluid homeostasis and sympathoexcitation in CHF. After implantation of intracerebroventricular (ICV) cannulae, myocardial infarction (MI) was induced in wild-type (WT) and KO mice by coronary artery ligation. Osmotic mini-pumps were implanted into one set of WT + MI/Sham mice for continuous ICV infusion of Etanercept (ETN), a TNF receptor fusion pro... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4383394 Wed, 19 Jan 2011 09:30:03 +0100 4383394 http://www.medworm.com/index.php?rid=4383393&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F92180x4w24551258%2F In conclusion, increased oxidative and nitrosative stress, coupled with lack of augmented SOD and catalase activities, contributes importantly to the exacerbating impact of pressure overload on MPT pore opening and cell death in ischemic-reperfused hearts. Content Type Journal ArticlePages 1-11DOI 10.1007/s00395-011-0150-7Authors Mahmood S. Mozaffari, Department of Oral Biology, CL-2134, School of Dentistry, Medical College of Georgia, Augusta, GA 30012-1128, USABabak Baban, Department of Oral Biology, CL-2134, School of Dentistry, Medical College of Georgia, Augusta, GA 30012-1128, USAJun Yao Liu, Department of Oral Biology, CL-2134, School of Dentistry, Medical College of Georgia, Augusta, GA 30012-1128, USAWorku Abebe, Department of Oral Biology, CL-2134, School of Dentistry, M... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4383393 Wed, 19 Jan 2011 09:30:03 +0100 4383393 http://www.medworm.com/index.php?rid=4378561&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj34m17730652l7m5%2F This study investigated the role of tissue inhibitor of metalloproteinase-3 (TIMP-3)/matrix metalloproteinase (MMP)/epidermal growth factor (EGF)/transforming growth factor (TGF)-β1 pathway in infarct healing and effects of cetuximab on cardiac rupture after MI. Induction of MI was achieved by left coronary artery ligation in wild-type (WT) and TIMP-3−/− mice. TIMP-3 deficiency resulted in a fourfold increase in cardiac rupture and 50% decrease in survival after MI. Hydroxyproline content, collagen synthesis and myofibroblast cell number in the infarct region, and the force required to induce rupture of the infarct scar were significantly decreased, while MMP activity was increased in TIMP-3−/− mice. EGF proteins were increased by threefold in TIMP-3−/− mice following MI, ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4378561 Tue, 18 Jan 2011 15:03:12 +0100 4378561 http://www.medworm.com/index.php?rid=4356367&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp031951725l175km%2F Abstract  Atrial fibrillation (AF) is a common complication in hyperthyroidism. Earlier studies demonstrate that thyroid hormone decreases L-type calcium channel (LCC) current expression with resultant shortening of action potential duration (APD), providing a substrate for AF. The aim of this study was to investigate the potential mechanism underlying the regulatory effect of thyroid hormone on LCC. In a hyperthyroid rat model, thyroid hormone (triiodothyronine [T3]) administration down-regulated atrial LCC expression. In vitro, treatment of murine atrial myocytes (HL-1) with T3 decreased the expression of LCC and its current, resulting in abbreviation of APD. Furthermore, T3 inhibited the activation of cyclic AMP response element (CRE)-binding protein (CREB), including ph... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4356367 Fri, 14 Jan 2011 16:32:50 +0100 4356367 http://www.medworm.com/index.php?rid=4300997&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq6056338106n5111%2F Abstract  The atria respond to various pathological stimuli including pressure and volume overload with remodeling and dilatation. Dilatation of the left atrium is associated with atrial fibrillation. The mechanisms involved in chamber-specific hypertrophy are largely unknown. Angiotensin II is hypothesized to take part in mediating this response. ATF3 is an immediate early gene found at the receiving end of multiple stress and growth stimuli. Here we characterize ATF3 as a direct target gene for angiotensin II. ATF3 expression is regulated by angiotensin receptor-mediated signaling in vivo and in vitro at the transcriptional level. ATF3 induction is mediated by cooperation between both the AT1A and AT2 receptor subtypes. While AT2R blocker (PD123319) efficiently blocks ATF3... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4300997 Wed, 29 Dec 2010 17:09:10 +0100 4300997 http://www.medworm.com/index.php?rid=4289150&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc114330125325v7r%2F Abstract  MicroRNAs (miRs) are small non-coding RNAs, which control gene expression either by inducing mRNA degradation or by blocking translation, and play a crucial role in tissue homeostasis. In the cardiovascular system, miRs were shown to control cardiac hypertrophy, fibrosis and apoptosis, angiogenesis, and vessel remodeling. In addition, miRs regulate stem cell maintenance and some miRs induced cell fate decisions. This review summarizes the current insights into the control of stem cells and lineage commitment by miRs focusing specifically to the regulation of endothelial, smooth muscle, and cardiac lineage. Content Type Journal ArticleDOI 10.1007/s00395-010-0139-7Authors Kisho Ohtani, Institute for Cardiovascular Regeneration, Center of Molecular Medicine, Un... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4289150 Thu, 23 Dec 2010 17:47:08 +0100 4289150 http://www.medworm.com/index.php?rid=4289151&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F815p72445n5515l8%2F Abstract  Cardiac lipid accumulation is associated with decreased cardiac function and energy status (PCr/ATP). It has been suggested that elevated plasma fatty acid (FA) concentrations are responsible for the cardiac lipid accumulation. Therefore, the aim of the present study was to investigate if elevating plasma FA concentrations by exercise results in an increased cardiac lipid content, and if this influences cardiac function and energy status. Eleven male subjects (age 25.4 ± 1.1 years, BMI 23.6 ± 0.8 kg/m2) performed a 2-h cycling protocol, once while staying fasted and once while ingesting glucose, to create a state of high versus low plasma FA concentrations, respectively. Cardiac lipid content was measured by proton magnetic resonance... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4289151 Wed, 22 Dec 2010 20:13:41 +0100 4289151 http://www.medworm.com/index.php?rid=4285719&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0302513739006758%2F Abstract  Postnatal vasculogenesis is mediated by endothelial progenitor cells (EPCs) which consist of subpopulations with different functional capacities. Our goal was to profile chemokine receptor expression on relevant subsets of EPCs and to characterize their role for effector functions. CD34+/CD133+/VEGFR2+ EPCs were characterized by high expression of chemokine receptors CXCR4, CX3CR1, BLT1, and low level expression of CXCR2 and CCR2, while primordial CD34−/CD133+/VEGFR2+ EPCs express these chemokine receptors at comparably low levels. Migration assays revealed that SDF-1, fractalkine, and LTB4 significantly increase migration of CD34−/CD133+/VEGFR2+ EPCs, while SDF-1 was the only potent agonist of migration of CD34+/CD133+/VEGFR2+ EPCs. SDF-1, fractalkine, and LTB4... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4285719 Mon, 20 Dec 2010 23:00:46 +0100 4285719 http://www.medworm.com/index.php?rid=4285720&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F773t169587x44614%2F Abstract  The pleiotropic cytokine oncostatin M (OSM), a member of the glycoprotein (gp)130 ligand family, plays a key role in inflammation and cardiovascular disease. As inflammation precedes and accompanies pathological angiogenesis, we investigated the effect of OSM and other gp130 ligands on vascular endothelial growth factor (VEGF) production in human vascular smooth muscle cells (SMC). Human coronary artery SMC (HCASMC) and human aortic SMC (HASMC) were treated with different gp130 ligands. VEGF protein was determined by ELISA. Specific mRNA was detected by RT-PCR. Western blotting was performed for signal transducers and activators of transcription1 (STAT1), STAT3, Akt and p38 mitogen-activated protein kinase (p38 MAPK). OSM mRNA and VEGF mRNA expression was analyzed... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4285720 Mon, 20 Dec 2010 22:53:25 +0100 4285720 http://www.medworm.com/index.php?rid=4285722&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm35n7411131u4q58%2F In conclusion, our results show for the first time that TG CaMKIIδC overexpression induces diastolic dysfunction and arrhythmogenic triggers possibly via an enhanced late I Na. Inhibition of elevated late I Na had beneficial effects on arrhythmias as well as diastolic function in papillary muscles from CaMKIIδC TG mice. Thus, late I Na inhibition appears to be a promising option for diastolic dysfunction and arrhythmias in HF where CaMKII is found to be increased. Content Type Journal ArticleDOI 10.1007/s00395-010-0136-xAuthors Samuel Sossalla, Department of Cardiology and Pneumology/Heart Center, Georg-August-University Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, GermanyUlrike Maurer, Department of Cardiology and Pneumology/Heart Center, Georg-August-University Göttin... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4285722 Mon, 20 Dec 2010 22:53:24 +0100 4285722 http://www.medworm.com/index.php?rid=4285721&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F648830736136l65u%2F In conclusion, short_ND improves post-ischemic myocardial performance in postconditioned hearts. However, long_ND increases myocardial susceptibility to I/R injury and abolishes cardioprotection by PostC. This increased susceptibility might be related to steroid-induced hypertrophy and/or to altered enzyme expression/phosphorylation. Content Type Journal ArticleDOI 10.1007/s00395-010-0143-yAuthors C. Penna, Department of Clinical and Biological Sciences, “S. Luigi Gonzaga” Hospital, University of Turin, Regione Gonzole 10, 10043 Orbassano (TO), ItalyF. Tullio, Department of Clinical and Biological Sciences, “S. Luigi Gonzaga” Hospital, University of Turin, Regione Gonzole 10, 10043 Orbassano (TO), ItalyM.-G. Perrelli, Department of Clinical and Biological Sciences, “S. L... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4285721 Mon, 20 Dec 2010 22:53:24 +0100 4285721 http://www.medworm.com/index.php?rid=4267305&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk01470738ht54674%2F Abstract  PDE4 isoenzymes are critical in the control of cAMP signaling in rodent cardiac myocytes. Ablation of PDE4 affects multiple key players in excitation–contraction coupling and predisposes mice to the development of heart failure. As little is known about PDE4 in human heart, we explored to what extent cardiac expression and functions of PDE4 are conserved between rodents and humans. We find considerable similarities including comparable amounts of PDE4 activity expressed, expression of the same PDE4 subtypes and splicing variants, anchoring of PDE4 to the same subcellular compartments and macromolecular signaling complexes, and downregulation of PDE4 activity and protein in heart failure. The major difference between the species is a fivefold higher amount of non... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4267305 Wed, 15 Dec 2010 19:11:38 +0100 4267305 http://www.medworm.com/index.php?rid=4267304&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu82750210w56m056%2F Content Type Journal ArticleDOI 10.1007/s00395-010-0140-1Authors Stephan B. Felix, Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität Greifswald, Friedrich-Loeffler Str. 23a, 17475 Greifswald, Germany Journal Basic Research in CardiologyOnline ISSN 1435-1803Print ISSN 0300-8428 (Source: Basic Research in Cardiology) Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4267304 Wed, 15 Dec 2010 19:11:38 +0100 4267304 http://www.medworm.com/index.php?rid=4225907&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5182782247541q26%2F Abstract  A chronic (auto)immune response is the critical mechanism in atherosclerosis. Interleukin-17A is a pivotal effector cytokine, which modulates immune cell trafficking and initiates inflammation in (auto)immune and infectious diseases. However, expression of IL-17A in the context of human atherosclerosis has hardly been explored. Carotid artery plaques were collected from 79 patients undergoing endarterectomy. Patients were grouped according to their symptomatic status (TIA, stroke), plaque morphology and medication. Quantitative RT-PCR was used to analyze tissue inflammation and immunohistochemistry to assess cellular source of IL-17A expression and lesion morphology. Carotid plaques from patients with ischemic symptoms were characterized by a highly activated infl... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4225907 Tue, 30 Nov 2010 06:59:14 +0100 4225907 http://www.medworm.com/index.php?rid=4225908&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl63x706247781342%2F Abstract  Human monocytes/macrophages express the angiotensin-converting enzyme (ACE) but nothing is known about its role under physiological conditions. As adipose tissue contains resident macrophages that have been implicated in the generation of insulin resistance in expanding fat mass, we determined whether adipocytes release factors that affect ACE expression and function in monocytes. Incubation of human monocyte-derived macrophages with conditioned medium from freshly isolated human adipocytes (BMI = 25.4 ± 0.96) resulted in a 4-fold increase in ACE expression. The effect was insensitive to denaturation and different proteases but abolished after lipid extraction. mRNA levels of the major histocompatibility complex class II protein increased in pa... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4225908 Tue, 30 Nov 2010 06:59:11 +0100 4225908 http://www.medworm.com/index.php?rid=4191546&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu508517767714525%2F In conclusion, the IPC effluent retains strong cardioprotective properties, containing hydrophobic mediator(s) < 30 kDa offering cytoprotection via PI3K/Akt-dependent signaling at ischemic reperfusion. Content Type Journal ArticleDOI 10.1007/s00395-010-0133-0Authors L. Breivik, Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, NorwayE. Helgeland, Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, NorwayE. K. Aarnes, Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, NorwayJ. Mrdalj, Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, NorwayA. K. Jonassen, Department of Biomedicine, Faculty of Medicine ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4191546 Sat, 20 Nov 2010 06:56:04 +0100 4191546 http://www.medworm.com/index.php?rid=4164840&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh21w8v424010l725%2F In conclusion, LA posterior myocytes contain a high arrhythmogenic potential and distinctive electrophysiological characteristics, which may contribute to the pathophysiology of AF. Content Type Journal ArticleDOI 10.1007/s00395-010-0132-1Authors Kazuyoshi Suenari, Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, JapanYao-Chang Chen, Department of Biomedical Engineering, National Defense Medical Center, Taipei, TaiwanYu-Hsun Kao, Division of Cardiovascular Medicine, Taipei Medical University-Wan Fang Hospital, 111, Hsin-Lung Road, Sec. 3, Taipei, TaiwanChen-Chuan Cheng, Division of Cardiology, Chi-Mei Medical Center, Tainan, TaiwanYung-Kuo Lin, Division of Cardiovascular Medicine, Taipei Medical University-Wan Fang Hospi... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4164840 Fri, 12 Nov 2010 08:49:18 +0100 4164840 http://www.medworm.com/index.php?rid=4160015&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flt341108477t93x5%2F Abstract  The M-band is the prominent cytoskeletal structure that cross-links the myosin and titin filaments in the middle of the sarcomere. To investigate M-band alterations in heart disease, we analyzed the expression of its main components, proteins of the myomesin family, in mouse and human cardiomyopathy. Cardiac function was assessed by echocardiography and compared to the expression pattern of myomesins evaluated with RT-PCR, Western blot, and immunofluorescent analysis. Disease progression in transgenic mouse models for dilated cardiomyopathy (DCM) was accompanied by specific M-band alterations. The dominant splice isoform in the embryonic heart, EH-myomesin, was strongly up-regulated in the failing heart and correlated with a decrease in cardiac function (R =&... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4160015 Wed, 10 Nov 2010 17:23:40 +0100 4160015 http://www.medworm.com/index.php?rid=4120449&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff3006x377v610205%2F In conclusion, direct inhibition of GSK-3β may provide an alternative strategy to protect diabetic hearts against I/R injury. Content Type Journal ArticleDOI 10.1007/s00395-010-0130-3Authors Nehmat Ghaboura, Protection et Remodelage du Myocarde, UPRES EA 3860, Faculté de Médecine, Université d’Angers, Rue Haute de Reculée, 49045 Angers Cedex 1, FranceSophie Tamareille, Protection et Remodelage du Myocarde, UPRES EA 3860, Faculté de Médecine, Université d’Angers, Rue Haute de Reculée, 49045 Angers Cedex 1, FrancePierre-Henri Ducluzeau, INSERM U694, Faculté de Médecine, Université d’Angers, Angers, FranceLinda Grimaud, INSERM U771, CNRS UMR 6214, Faculté de Médecine, Université d’Angers, Angers, FranceLaurent Loufrani, INSERM U771, CNRS UMR 6214, Faculté de M�... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4120449 Wed, 27 Oct 2010 15:59:28 +0100 4120449 http://www.medworm.com/index.php?rid=4120450&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh75853u317h61504%2F In conclusion, TASK-1 plays a functional role in the repolarization of the cardiac action potential in vivo and contributes to the maintenance of HRV. Content Type Journal ArticleDOI 10.1007/s00395-010-0128-xAuthors Birgit C. Donner, Department of Pediatric Cardiology and Pneumology, University Children′s Hospital, Moorenstrasse 5, 40225 Düsseldorf, GermanyMartina Schullenberg, Department of Pediatric Cardiology and Pneumology, University Children′s Hospital, Moorenstrasse 5, 40225 Düsseldorf, GermanyNora Geduldig, Department of Pediatric Cardiology and Pneumology, University Children′s Hospital, Moorenstrasse 5, 40225 Düsseldorf, GermanyAnja Hüning, Department of Pediatric Cardiology and Pneumology, University Children′s Hospital, Moorenstrasse 5, 40225 Düsseldorf, Ge... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4120450 Tue, 26 Oct 2010 16:45:52 +0100 4120450 http://www.medworm.com/index.php?rid=4109817&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F44h6v54450w4w146%2F Abstract  Protease-activated receptor-2 (PAR2) is expressed in endothelial cells and mediates endothelium-dependent vasodilation. We hypothesized that PAR2 regulates tumor necrosis factor-alpha (TNF-α)-induced coronary arteriolar dysfunction in type 2 diabetic (db/db) mice. To test this, coronary arterioles from WT control, db/db, db/db mice treated with PAR2 antagonist FSLLRY–NH2 (db/db+FSLLRY–NH2) and db/db mice null for TNF (dbTNF−/dbTNF−) were isolated and pressurized (60 cmH2O) without flow. Although vasodilation to the endothelium-independent vasodilator sodium nitroprusside (SNP) was not different among WT, db/db, db/db+FSLLRY–NH2 and dbTNF−/dbTNF−, endothelium-dependent acetylcholine (ACh)- and flow-mediated vasodilation were impaired in db/db mice ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4109817 Sun, 24 Oct 2010 05:33:09 +0100 4109817 http://www.medworm.com/index.php?rid=4089519&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F070g0285h3057t75%2F We present here adverse myocardial remodeling due to a chronic lack of TLR2 expression. Myocardial ischemia/reperfusion (MI/R) was surgically induced in C3HeN-mice by ligation of the left anterior descending coronary artery for 20 min, followed by 24 h or 28 days of reperfusion. TLR2−/−-mice and TLR2-Ab treated (T2.5) WT-mice displayed a reduction of infarct size, plasma troponin T concentrations, and leukocyte infiltration as compared with untreated controls after 24 h of reperfusion. After 28 days, however, magnetic resonance imaging revealed a marked left ventricular dilation in TLR2−/−-animals, which was associated with pronounced matrix remodeling characterized by reduced collagen and decorin density in the infarct scar. Our data show adverse effe... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4089519 Thu, 21 Oct 2010 17:14:43 +0100 4089519 http://www.medworm.com/index.php?rid=4089520&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq0882433rl12kh43%2F Abstract  The signal transducer and activator of transcription 3 (STAT3) contributes to cardioprotection by ischemic pre- and postconditioning. Mitochondria are central elements of cardioprotective signaling, most likely by delaying mitochondrial permeability transition pore (MPTP) opening, and STAT3 has recently been identified in mitochondria. We now characterized the mitochondrial localization of STAT3 and its impact on respiration and MPTP opening. STAT3 was mainly present in the matrix of subsarcolemmal and interfibrillar cardiomyocyte mitochondria. STAT1, but not STAT5 was also detected in mitochondria under physiological conditions. ADP-stimulated respiration was reduced in mitochondria from mice with a cardiomyocyte-specific deletion of STAT3 (STAT3-KO) versus wildty... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4089520 Tue, 19 Oct 2010 23:50:04 +0100 4089520 http://www.medworm.com/index.php?rid=4089521&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0786j0447257gm1h%2F Abstract  The aim of this study was to investigate the prognostic value of circulating troponin I (TNI)-autoantibodies in plasma of patients with chronic heart failure. Sera of 390 heart failure patients were tested for the presence of anti-TNI antibodies by enzyme-linked immunosorbent assay (ELISA), including 249 (63.8% of total) patients with dilated cardiomyopathy (DCM) and 141 (36.2% of total) patients with ischemic cardiomyopathy (ICM). A total of 72 patients (18.5% of total) were female and 318 (81.5% of total) were male. Mean patient age was 54.6 ± 11.3 years and mean follow-up time was 3.8 ± 3.2 years. TNI-autoantibodies (titer of ≥1:40) were detected in 73 out of 390 patients (18.7% of total). In TNI-autoantibody positive patients m... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4089521 Tue, 19 Oct 2010 23:36:33 +0100 4089521 http://www.medworm.com/index.php?rid=4068270&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb51k83p1302x3258%2F Abstract  Ethanolamine is a biogenic amine found naturally in the body as part of membrane lipids and as a metabolite of the cardioprotective substances, sphingosine-1-phosphate (S1P) and anandamide. In the brain, ethanolamine, formed from the breakdown of anandamide protects against ischaemic apoptosis. However, the effects of ethanolamine in the heart are unknown. Signal transducer and activator of transcription 3 (STAT-3) is a critical prosurvival factor in ischaemia/reperfusion (I/R) injury. Therefore, we investigated whether ethanolamine protects the heart via activation of STAT-3. Isolated hearts from wildtype or cardiomyocyte specific STAT-3 knockout (K/O) mice were pre-treated with ethanolamine (Etn) (0.3 mmol/L) before I/R insult. In vivo rat hearts were subje... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4068270 Mon, 11 Oct 2010 16:46:15 +0100 4068270 http://www.medworm.com/index.php?rid=4026159&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj8827112x8w7w470%2F Abstract  Studies on the role of mitochondrial fission/fusion (MFF) proteins in the heart have been initiated recently due to their biological significance in cell metabolism. We hypothesized that the expression of MFF proteins is affected by post-infarction remodeling and in vitro cardiomyocyte hypertrophy, and serves as a target for the Na+/H+ exchanger 1 (NHE-1) inhibition. Post-infarction remodeling was induced in Sprague–Dawley rats by coronary artery ligation (CAL) while in vitro hypertrophy was induced in cardiomyocytes by phenylephrine (PE). Mitochondrial fission (Fis1, DRP1) and fusion (Mfn2, OPA1) proteins were analyzed in heart homogenates and cell lysates by Western blotting. Our results showed that 12 and 18 weeks after CAL, Fis1 increased by 80% (P ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4026159 Fri, 01 Oct 2010 07:13:40 +0100 4026159 http://www.medworm.com/index.php?rid=4026158&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjqnl838l1052k261%2F Abstract  MicroRNAs (miRNAs) are important regulators of adaptive and maladaptive responses in cardiovascular diseases and hence are considered to be potential therapeutical targets. However, their role as novel biomarkers for the diagnosis of cardiovascular diseases still needs to be systematically evaluated. We assessed here for the first time whole-genome miRNA expression in peripheral total blood samples of patients with acute myocardial infarction (AMI). We identified 121 miRNAs, which are significantly dysregulated in AMI patients in comparison to healthy controls. Among these, miR-1291 and miR-663b show the highest sensitivity and specificity for the discrimination of cases from controls. Using a novel self-learning pattern recognition algorithm, we identified a uniq... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=4026158 Fri, 01 Oct 2010 07:13:40 +0100 4026158 http://www.medworm.com/index.php?rid=3999551&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj1r72248597u5182%2F Abstract  Ischemic heart disease (IHD) is the leading cause of death worldwide. Novel cardioprotective strategies are therefore required to improve clinical outcomes in patients with IHD. Although a large number of novel cardioprotective strategies have been discovered in the research laboratory, their translation to the clinical setting has been largely disappointing. The reason for this failure can be attributed to a number of factors including the inadequacy of the animal ischemia–reperfusion injury models used in the preclinical cardioprotection studies and the inappropriate design and execution of the clinical cardioprotection studies. This important issue was the main topic of discussion of the UCL-Hatter Cardiovascular Institute 6th International Cardioprotection W... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3999551 Thu, 23 Sep 2010 17:18:19 +0100 3999551 http://www.medworm.com/index.php?rid=3995153&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F22v8x7100n180207%2F Abstract  Current concepts of vascular permeability are largely still based on the Starling principle of 1896. Starling’s contribution to understanding vascular fluid homeostasis comes from realising that the transport of fluid to and from the interstitial space of peripheral tissues follows the balance between opposing oncotic and hydrostatic pressures. It is presumed that in peripheral tissues fluid is readily filtered from blood to tissues at the arterial/arteriolar side of the circulation and largely reabsorbed at the venular/venous aspect, excess fluid being removed from the tissue by the lymphatic system. This balance is determined particularly by the properties of the vascular barrier. Recent studies have shown that the endothelial glycocalyx, located with a thickn... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3995153 Tue, 21 Sep 2010 18:06:57 +0100 3995153 http://www.medworm.com/index.php?rid=3995154&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk177t68102t864j7%2F Abstract  Sca-1 and VEGFR-2 positive pro-angiogenic cells (PAC) predict outcome of patients with vascular disease. Activation of the renin–angiotensin–aldosterone system impairs PAC function. The effects of the direct renin inhibitor aliskiren on PAC numbers and function are not known. Treatment of C57Bl/6 mice and Apo E−/− mice on high-cholesterol diet with aliskiren, 25 mg/kg/day s.c. for 3–6 weeks, reduced systolic and diastolic blood pressure by −11.5 and −13.7% compared to vehicle. Aliskiren increased Sca-1/VEGFR-2 positive PAC in the blood (159 ± 14%) and spleen-derived DiLDL/lectin positive PAC (180 ± 21%). Migratory capacity of PAC was increased to 165 ± 16%. In cultured human PAC, aliskiren dose-dependently in... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3995154 Mon, 20 Sep 2010 19:38:57 +0100 3995154 http://www.medworm.com/index.php?rid=3989215&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk4g886vvhx305811%2F Abstract  Histamine has a positive inotropic effect on ventricular myocardium and stimulation of histamine H2 receptors increases the intracellular cAMP level via Gs protein, as dose stimulation of β-adrenergic receptors, and worsens heart failure. To test whether a histamine H2 receptor blocker had a beneficial effect in addition to β-adrenergic receptor blockade, we investigated the cardioprotective effect of famotidine, a histamine H2 receptor blocker, in dogs receiving a β-blocker. We induced heart failure in dogs by rapid ventricular pacing (230 beats/min). Animals received no drugs (control group), famotidine (1 mg/kg daily), carvedilol (0.1 mg/kg daily), or carvedilol plus famotidine. Both cardiac catheterization and echocardiography were performed before ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3989215 Sat, 18 Sep 2010 05:49:18 +0100 3989215 http://www.medworm.com/index.php?rid=3955654&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh2884ju01517414q%2F Abstract  Endothelial progenitor cells (EPCs) contribute to the process of reendothelialization and prevent neointimal formation after vascular injury. The present study was designed to investigate whether the cysteine-rich 61 (CYR61, CCN1), an important matricellular component of local vascular microenvironment, has effect on EPCs differentiation and reendothelialization in response to vascular injury in rat. Following balloon injury, CCN1 was rapidly induced and dynamically changed at vascular lesions. Overexpression of CCN1 by adenovirus (Ad-CCN1) accelerated reendothelialization and inhibited neointimal formation in the early phase (day 14) after vascular injury (p < 0.05), while no effect was shown on day 21. Ad-CCN1 treatment increased the adhering EPCs on... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3955654 Thu, 09 Sep 2010 16:43:04 +0100 3955654 http://www.medworm.com/index.php?rid=3889793&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1272mu3465rr8420%2F Abstract  Protein kinase D (PKD) targets several proteins in the heart, including cardiac troponin I (cTnI) and class II histone deacetylases, and regulates cardiac contraction and hypertrophy. In adult rat ventricular myocytes (ARVM), PKD activation by endothelin-1 (ET1) occurs via protein kinase Cε and is attenuated by cAMP-dependent protein kinase (PKA). Intracellular compartmentalisation of cAMP, arising from localised activity of distinct cyclic nucleotide phosphodiesterase (PDE) isoforms, may result in spatially constrained regulation of the PKA activity that inhibits PKD activation. We have investigated the roles of the predominant cardiac PDE isoforms, PDE2, PDE3 and PDE4, in PKA-mediated inhibition of PKD activation. Pretreatment of ARVM with the non-selective PDE... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3889793 Fri, 20 Aug 2010 05:47:03 +0100 3889793 http://www.medworm.com/index.php?rid=3873808&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa6435l401vn4754t%2F In conclusion, mechanical load leads to an upregulation of SERCA expression. This is followed by upregulation of natriuretic peptides with subsequent suppression of SERCA upregulation. Elevated natriuretic peptides may suppress SERCA expression by inhibition of calcineurin activity via activation of GC-A. Content Type Journal ArticleDOI 10.1007/s00395-010-0115-2Authors Karl Toischer, Abteilung Kardiologie und Pneumologie, Georg-August-Universität, Robert-Koch-Str. 40, 37075 Göttingen, GermanyNils Teucher, Abteilung Herz-, Thorax- und Gefäßchirurgie, Georg-August-Universität, Göttingen, GermanyBernhard Unsöld, Abteilung Kardiologie und Pneumologie, Georg-August-Universität, Robert-Koch-Str. 40, 37075 Göttingen, GermanyMichaela Kuhn, Physiologisches Institut, Universität W... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3873808 Sat, 14 Aug 2010 08:36:41 +0100 3873808 http://www.medworm.com/index.php?rid=3865954&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe6w522744783083h%2F In conclusion, HMGB1 plays a major role in DM and post-I/R remodeling by binding to RAGE, resulting in activation of sustained pro-inflammatory pathways and enhanced myocardial injury. Therefore, blockage of HMGB1 might represent a therapeutic strategy to reduce post-ischemic remodeling in DM. Content Type Journal ArticleDOI 10.1007/s00395-010-0114-3Authors H. Christian Volz, Department of Medicine III, University of Heidelberg, INF 410, 69120 Heidelberg, GermanyCathrin Seidel, Department of Medicine III, University of Heidelberg, INF 410, 69120 Heidelberg, GermanyDanai Laohachewin, Department of Medicine III, University of Heidelberg, INF 410, 69120 Heidelberg, GermanyZiya Kaya, Department of Medicine III, University of Heidelberg, INF 410, 69120 Heidelberg, GermanyOliver J. Mül... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3865954 Wed, 11 Aug 2010 21:22:26 +0100 3865954 http://www.medworm.com/index.php?rid=3818096&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F873427p5gg048755%2F Abstract  Our novel proposal is that TNFα exerts a direct effect on mitochondrial respiratory function in the heart, independently of its cell surface receptors. TNFα-induced cardioprotection is known to involve reactive oxygen species (ROS) and sphingolipids. We therefore further propose that this direct mitochondrial effect is mediated via ROS and sphingolipids. The protective concentration of TNFα (0.5 ng/ml) was added to isolated heart mitochondria from black 6 × 129 mice (WT) and double TNF receptor knockout mice (TNFR1&2−/−). Respiratory parameters and inner mitochondrial membrane potential were analyzed in the presence/absence of two antioxidants, N-acetyl-l-cysteine or N-tert-butyl-α-(2-sulfophenyl)nitrone or two antagonists of the sphingolipi... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3818096 Mon, 02 Aug 2010 19:18:51 +0100 3818096 http://www.medworm.com/index.php?rid=3796158&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv7214172qh543v53%2F Abstract  Circadian rhythms influence the incidence of adverse cardiac events but the underlying mechanisms are not well defined. We sought to investigate the role of the β3-adrenoceptor (β3-AR) in cardiac circadian disorders and arrhythmia severity after myocardial infarction (MI). MI was created by ligating the left anterior descending coronary artery of the rat heart in situ. Circadian variations of the myocardial expressions of β3-AR and clock genes Bmal1 and Npas2 were examined by real time reverse transcription polymerase chain reaction, Western blot and immunohistochemistry. Electrocardiograms and myocardial contraction were recorded in vivo and/or ex vivo. Ventricular tachyarrhythmias were induced by isoprenaline. Normal rats showed circadian oscillations in both... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3796158 Mon, 26 Jul 2010 22:09:50 +0100 3796158 http://www.medworm.com/index.php?rid=3785064&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqr3210112l005005%2F In conclusion, clustering in CSs leads to the induction of a muscle-specific functional response in about 30% of CPCs; this is accompanied by development of a cardiac-specific expression pattern. Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-010-0111-6Authors C. Altomare, University of Milano-Bicocca Department of Biotechnologies and Biosciences p.za della Scienza 2 20126 Milan ItalyL. Barile, University of Milano-Bicocca Department of Biotechnologies and Biosciences p.za della Scienza 2 20126 Milan ItalyS. Marangoni, University of Milano-Bicocca Department of Biotechnologies and Biosciences p.za della Scienza 2 20126 Milan ItalyM. Rocchetti, University of Milano-Bicocca Department of Biotechnologies and Biosciences p.za della Scienza 2 20126 Milan It... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3785064 Fri, 23 Jul 2010 12:25:18 +0100 3785064 http://www.medworm.com/index.php?rid=3785065&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fgh06203447201242%2F Abstract  Diabetes is characterized by a chronic stage of hyperglycemia associated with endothelial progenitor cell dysfunction and reduced neovascularization in response to tissue ischemia. The underlying mechanisms are not entirely clear. The bone marrow niches provide the essential microenvironment for maintenance of stem cell function in the bone marrow. A disturbed stem cell niche might lead to stem cell dysfunction, thereby, impairing progenitor cell-dependent vascular repair. Therefore, we investigated the effects of streptozotocin-induced diabetes on the bone marrow stem cell niches and stem cell function in mice. Here, we show that long-term diabetes induced a reduction in Lin−Sca-1+c-kit+ hematopoietic progenitor cells and reduced the repopulation capacity in a c... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3785065 Fri, 23 Jul 2010 12:25:17 +0100 3785065 http://www.medworm.com/index.php?rid=3785066&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0654022760936743%2F Abstract  High-density lipoproteins (HDL) are the major plasma carriers for sphingosine 1-phosphate (S1P) in healthy individuals, but their S1P content is unknown for patients with coronary artery disease (CAD). The aim of the study was to determine whether the S1P levels in plasma and HDL are altered in coronary artery disease. S1P was determined in plasma and HDL isolated by ultracentrifugation from patients with myocardial infarction (MI, n = 83), stable CAD (sCAD, n = 95), and controls (n = 85). In our study, total plasma S1P levels were lower in sCAD than in controls (305 vs. 350 pmol/mL). However, normalization to HDL-cholesterol (a known determinant of plasma S1P) revealed higher normalized plasma S1P levels in sCAD than in controls ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3785066 Fri, 23 Jul 2010 12:25:16 +0100 3785066 http://www.medworm.com/index.php?rid=3673503&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fur146158728508r8%2F This study shows a new and protective role of TGF-β1-dependent up-regulation of the 37/67 LR in cardiomyocytes in cardiac remodelling with increased laminin expression. Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-010-0108-1Authors Sibylle Wenzel, Justus-Liebig-University Institute of Physiology Giessen GermanyKirsten Henning, Justus-Liebig-University Institute of Physiology Giessen GermanyAndreas Habbig, Justus-Liebig-University Institute of Physiology Giessen GermanySvenja Forst, Justus-Liebig-University Institute of Physiology Giessen GermanyRolf Schreckenberg, Justus-Liebig-University Institute of Physiology Giessen GermanyJacqueline Heger, Justus-Liebig-University Institute of Physiology Giessen GermanyHagen Maxeiner, University Hospital Giesse... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3673503 Thu, 17 Jun 2010 11:25:51 +0100 3673503 http://www.medworm.com/index.php?rid=3649768&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc68u6770404t0128%2F Content Type Journal ArticleCategory Invited EditorialDOI 10.1007/s00395-010-0107-2Authors Katrin Wittköpper, University Medical Center Göttingen, Georg August University Göttingen Department of Pharmacology Robert-Koch-Str. 40 37075 Göttingen GermanyThomas Eschenhagen, University Medical Center Hamburg Eppendorf Department of Experimental and Clinical Pharmacology Hamburg GermanyAli El-Armouche, University Medical Center Göttingen, Georg August University Göttingen Department of Pharmacology Robert-Koch-Str. 40 37075 Göttingen Germany Journal Basic Research in CardiologyOnline ISSN 1435-1803Print ISSN 0300-8428 (Source: Basic Research in Cardiology) Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3649768 Mon, 07 Jun 2010 19:29:51 +0100 3649768 http://www.medworm.com/index.php?rid=3626904&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv255x07h5300mg06%2F Abstract  Cardiac apoptosis has been considered an important contributing factor to heart failure. Several subcellular mechanisms, including increased protein phosphatase 1 activity, have been suggested to induce apoptosis. Protein phosphatase 1 is regulated by an endogenous inhibitor-1 (I-1) that is activated upon phosphorylation at threonine 35 via protein kinase A. Here, we tested whether cardiac-specific overexpression of a constitutively active (T35D, AA 1-65) inhibitor-1 (I-1c), could also affect cardiac apoptosis and heart failure progression induced by prolonged β-adrenergic stimulation. We found that either acute or chronic expression of I-1c reduced isoproterenol (ISO)-induced apoptosis assessed by nuclear condensation, TUNEL staining and DNA fragmentation. The b... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3626904 Sat, 29 May 2010 16:53:46 +0100 3626904 http://www.medworm.com/index.php?rid=3611039&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm1nn2ku05x3212v2%2F In conclusion, the present findings demonstrate for the first time that exercise training in CHF reverses CAC dysfunction and increases numbers of CD34+/KDR+ EPC, which is accompanied by improvement of peripheral endothelial function. The acute exercise-induced changes in CAC function wane with exercise training, suggesting that repetitive exercise bouts progressively lead to functional endothelial repair. Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-010-0105-4Authors Emeline M. Van Craenenbroeck, Antwerp University Hospital Department of Cardiology Wilrijkstraat 10 2650 Edegem BelgiumVicky Y. Hoymans, Antwerp University Hospital Laboratory of Cellular and Molecular Cardiology Edegem BelgiumPaul J. Beckers, Antwerp University Hospital Department of ... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3611039 Thu, 27 May 2010 16:55:57 +0100 3611039 http://www.medworm.com/index.php?rid=3600751&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy546133118152161%2F Abstract  Remote ischemic preconditioning (RIPC) with transient upper limb ischemia reduces myocardial injury in patients undergoing on-pump coronary artery bypass grafting (CABG) with cross-clamp fibrillation or blood cardioplegia for myocardial protection. Whether or not such protection is still operative when standard crystalloid cardioplegic arrest is used is uncertain. Fifty-three consecutive, non-diabetic patients with triple-vessel disease and 64 ± 12 years of age (mean ± SD), who underwent elective CABG surgery with crystalloid (Bretschneider) cardioplegic arrest, were allocated in a prospective, randomized, single-blinded protocol to receive either a RIPC protocol (3 cycles of 5 min transient left upper arm ischemia induced by inflati... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3600751 Fri, 21 May 2010 21:02:37 +0100 3600751 http://www.medworm.com/index.php?rid=3567456&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F376m313k63l30863%2F In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum. Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-010-0103-6Authors Enrico Lupia, University of Turin Department of Clinical Pathophysiology Via Genova 3 10126 Turin ItalyTiziana Spatola, University of Turin Department of Clinical Pathophysiology Via Genova 3 10126 Turin ItalyAlessandra Cuccurullo, University of Turin Department of Clinical Pathophysiology Via Genova 3 10126 Turin ItalyOrnella Bosco, University of Turin Department of Clinical Pathophysiology Via Genova 3 10126 Turin ItalyFilippo Mariano, CTO Hospital Department of Medicine Area, Nephrology and Dialysis Unit Turin ItalyAngela Pucci, Regina Margherit... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3567456 Fri, 14 May 2010 09:20:53 +0100 3567456 http://www.medworm.com/index.php?rid=3546222&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd228810p2137v377%2F In conclusion, remote limb ischaemic preconditioning reduced myocardial infarct size in the mice in a manner which implicates both a neural and humoral pathway. Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-010-0099-yAuthors Shiang Y. Lim, University College London Hospital and Medical School The Hatter Cardiovascular Institute 67 Chenies Mews London WC1E 6HX UKDerek M. Yellon, University College London Hospital and Medical School The Hatter Cardiovascular Institute 67 Chenies Mews London WC1E 6HX UKDerek J. Hausenloy, University College London Hospital and Medical School The Hatter Cardiovascular Institute 67 Chenies Mews London WC1E 6HX UK Journal Basic Research in CardiologyOnline ISSN 1435-1803Print ISSN 0300-8428 (Source: Basic Research in... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3546222 Fri, 07 May 2010 08:16:23 +0100 3546222 http://www.medworm.com/index.php?rid=3495252&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn2505w802666150v%2F Abstract  There is a growing need for pharmacological agents to manage cardiovascular disease in the rapidly growing elderly population. Here, we determine if acetaminophen is efficacious in decreasing age-related increases in cardiac reactive oxygen species (ROS) and apoptosis in aging Fischer 344 X Brown Norway rats. Compared to 6-month control animals, indices of oxidative (superoxide anion [O2 •–] and 4-hydroxy-2-nonenal [4-HNE]) and nitrosative (protein nitrotyrosylation) stress were markedly increased in 33-month-old rat hearts. 33-month animals that had been treated with acetaminophen (30 mg/kg/day p.o. for 6 months) exhibited diminished age-related increases in cardiac ROS levels and TUNEL positive nuclei and these changes were accompanied by improveme... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3495252 Wed, 21 Apr 2010 08:57:54 +0100 3495252 http://www.medworm.com/index.php?rid=3481469&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4487wqj0l3x32121%2F Abstract  The adult heart has been recently recognized as a self-renewing organ that contains a pool of committed resident cardiac stem cells (CSCs) and cardiac progenitor cells (CPCs). These adult CSCs and CPCs can be induced by cytokines and growth factors to migrate, differentiate, and proliferate in situ and potentially replace lost cardiomyocytes. Ligand-receptor systems, such as the tyrosine kinase receptor mesenchymal–epithelial transition factor (Met) and its ligand hepatocyte growth factor (HGF), are potential candidates for boosting migration, engraftment and commitment of CSCs. Here, we discuss the possible application of HGF/Met gene therapy to enhance the ability of CSCs to promote myocardial regeneration. Content Type Journal ArticleCategory ReviewDOI 10... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3481469 Wed, 14 Apr 2010 16:50:41 +0100 3481469 http://www.medworm.com/index.php?rid=3450685&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk3t5258p5315173r%2F Abstract  Beta-catenin is a component of the intercalated disc in cardiomyocytes, but can also be involved in signalling and activation of gene transcription. We wanted to determine how long-term changes in beta-catenin expression levels would affect mature cardiomyocytes. Conditional transgenic mice that either lacked beta-catenin or that expressed a non-degradable form of beta-catenin in the adult ventricle were created. While mice lacking beta-catenin in the ventricle do not have an overt phenotype, mice expressing a non-degradable form develop dilated cardiomyopathy and do not survive beyond 5 months. A detailed analysis could reveal that this phenotype is correlated with a distinct localisation of beta-catenin in adult cardiomyocytes, which cannot be detected in t... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3450685 Wed, 07 Apr 2010 19:18:15 +0100 3450685 http://www.medworm.com/index.php?rid=3450686&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ffu21739233753765%2F Abstract  Although the contribution of Wnt signaling in infarct healing is suggested, its exact role after myocardial infarction (MI) still needs to be unraveled. We evaluated the cardiac presence of active Wnt signaling in vivo following MI, and investigated in which cell types active Wnt signaling was present by determining Axin2 promoter-driven LacZ expression. C57BL/6 Axin2-LacZ reporter mice were sacrificed at days 0, 1, 3, 7, 14, and 21 after LAD ligation. Hearts were snap-frozen for immunohistochemistry (IHC) or enzymatically digested to obtain a single cell suspension for flow cytometric analysis. For both FACS and IHC, samples were stained for β-galactosidase and antibodies against Sca-1, CD31, ckit, and CD45. Active Wnt signaling increased markedly in the myocard... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3450686 Wed, 07 Apr 2010 06:50:22 +0100 3450686 http://www.medworm.com/index.php?rid=3445012&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk367348631057361%2F Abstract  Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that CD4-positive lymphocytes express the nuclear transcription factors Liver-X-Receptor (LXR) alpha and beta with an effect of LXR activators on TH1-cytokine release from these cells. However, the role of LXR in lymphocyte migration remains currently unexplored. Therefore, the present study investigated whether LXR activation might modulate chemokine-induced migration of these cells. Stimulation of CD4-positive lymphocytes with SDF-1 leads to a 2.5 ± 0.8-fold increase in cell migration (P < 0.05; n = 12). Pretreatment of cells with the LXR activator T0901317 reduces this effect in a concentration-dependent manner to a... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3445012 Sat, 03 Apr 2010 07:13:00 +0100 3445012 http://www.medworm.com/index.php?rid=3435940&cid=s_33458_7_f&fid=33458&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc061n453273j231v%2F Abstract  Inhibition of the cannabinoid receptor CB1 (CB1-R) exerts numerous positive cardiovascular effects such as modulation of blood pressure, insulin sensitivity and serum lipid concentrations. However, direct vascular effects of CB1-R inhibition remain unclear. CB1-R expression was validated in vascular smooth muscle cells (VSMCs) and aortic tissue of mice. Apolipoprotein E-deficient (ApoE−/−) mice were treated with cholesterol-rich diet and the selective CB1-R antagonist rimonabant or vehicle for 7 weeks. CB1-R inhibition had no effect on atherosclerotic plaque development, collagen content and macrophage infiltration but led to improved aortic endothelium-dependent vasodilation and decreased aortic reactive oxygen species (ROS) production and NADPH oxidase ac... Basic Research in Cardiology journals http://www.medworm.com/rss/comments.php?id=3435940 Fri, 02 Apr 2010 08:47:10 +0100 3435940