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 'Journal of Molecular and Cellular Cardiology' source. Tue, 07 Feb 2012 08:48:59 +0100 http://www.medworm.com/index.php?rid=5626293&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282812000120%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626293 Wed, 25 Jan 2012 15:45:23 +0100 5626293 http://www.medworm.com/index.php?rid=5535532&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100472X%2Fabstract%3Frss%3Dyes There is an error in the acknowledgments of the NIH grants supporting the research reported in the article referenced above. The NIH grant supporting the work of Paul S. Brookes is HL-071158, not HL-07115. The Acknowledgments section should read as follows: (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535532 Mon, 28 Nov 2011 05:00:00 +0100 5535532 http://www.medworm.com/index.php?rid=5535527&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004743%2Fabstract%3Frss%3Dyes Abstract: MicroRNAs (miRNAs) are noncoding RNAs that impact almost every aspect of biology and disease. Until now, the cell-specific effects of miRNAs in cardiovascular system have not been established. In the current study, the cellular functions of miR-221 and miR-222 (miR-221/222) in vascular smooth muscle cells (VSMCs) and vascular endothelial cells (ECs) were compared. In cultured cells, we identified that the effects of miR-221/222 on proliferation, migration, and apoptosis are opposite between VSMCs and ECs. In VSMCs, miR-221/222 had effects of pro-proliferation, pro-migration, and anti-apoptosis. In contrast, miR-221/222 had effects of anti-proliferation, anti-migration, and pro-apoptosis in ECs. The different expression profiles of their target genes, p27(Kip1), p57(kip2), and c-k... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535527 Wed, 23 Nov 2011 05:00:00 +0100 5535527 http://www.medworm.com/index.php?rid=5535525&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004718%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled ‘Possible Editorial’.Highlights: ► CORM-3 activates stress-responsive transcription factors in the heart. ► CORM-3 upregulates several cardioprotective molecules. ► CORM-3 attenuates the mitochondria-dependent apoptotic pathway. ► CORM-3 attenuates the death-receptor-mediated apoptotic pathway. ► CORM-3 induces a late PC-mimetic cardioprotective milieu in the heart. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535525 Mon, 21 Nov 2011 05:00:00 +0100 5535525 http://www.medworm.com/index.php?rid=5535533&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004688%2Fabstract%3Frss%3Dyes The article referenced above is a Rapid Communication. Due to a publishing error, this article was published as a Regular Article. The publisher would like to apologize for any inconvenience caused. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535533 Thu, 17 Nov 2011 05:00:00 +0100 5535533 http://www.medworm.com/index.php?rid=5535516&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100469X%2Fabstract%3Frss%3Dyes We report that SOCE is abundant and robust in neonatal cardiomyocytes; however, SOCE is absent from adult cardiomyocytes. Levels of STIM1 transcript and protein correlate with the amplitude of SOCE, and manipulation of STIM1 protein levels (via shRNA) or activity (via expression of constitutively active or dominant-negative mutants) reveals a critical role for STIM1 in activating SOCE in cardiac myocytes. In neonatal hearts a recently identified STIM1 splice variant (STIM1L) is predominant but diminishes with maturation, only to reemerge with agonist- or afterload-induced cardiac stress. To test for pathophysiological relevance, we evaluated both in vitro and in vivo models of cardiac hypertrophy, finding that STIM1 expression is re-activated by pathological stress to trigger significant S... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535516 Tue, 15 Nov 2011 05:00:00 +0100 5535516 http://www.medworm.com/index.php?rid=5535530&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004676%2Fabstract%3Frss%3Dyes Abstract: Remodeling of the cardiac extracellular matrix (ECM) is an integral part of wound healing and ventricular adaptation after myocardial infarction (MI), but the underlying mechanisms remain incompletely understood. Fibulin-2 is an ECM protein upregulated during cardiac development and skin wound healing, yet mice lacking fibulin-2 do not display any identifiable phenotypic abnormalities. To investigate the effects of fibulin-2 deficiency on ECM remodeling after MI, we induced experimental MI by permanent coronary artery ligation in both fibulin-2 null and wild-type mice. Fibulin-2 expression was up-regulated at the infarct border zone of the wild-type mice. Acute myocardial tissue responses after MI, including inflammatory cell infiltration and ECM protein synthesis and deposition ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535530 Thu, 10 Nov 2011 05:00:00 +0100 5535530 http://www.medworm.com/index.php?rid=5535519&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004640%2Fabstract%3Frss%3Dyes Abstract: Sex differences exist in the hypertrophic response, cardiac remodeling, and transition to heart failure of hypertensive patients, and while some of these differences are likely influenced by estrogen, the genetic pathways downstream of estrogen that impact on cardioprotection have yet to be fully elucidated. We have previously shown that the cardioprotective effects of adrenomedullin (AM), an emerging clinical biomarker for cardiovascular disease severity, vary with sex in mouse models. AM signaling during cardiovascular stress is strongly modulated by receptor activity-modifying protein 3 (RAMP3) via its interaction with the G protein-coupled receptor calcitonin receptor-like receptor (CLR). Like AM, RAMP3 expression is potently regulated by estrogen, and so we sought to determi... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535519 Mon, 07 Nov 2011 05:00:00 +0100 5535519 http://www.medworm.com/index.php?rid=5535515&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004652%2Fabstract%3Frss%3Dyes Abstract: Pressure overload induced heart failure affects cardiac mitochondrial function and leads to decreased respiratory capacity during contractile dysfunction. A similar cardiac mitochondrial dysfunction has been demonstrated by studies which induce heart failure through myocardial infarction or pacing. These heart failure models differ in their loading conditions to the heart and show nevertheless the same cardiac mitochondrial changes. Based on these observations we speculated that a workload independent mechanism may be responsible for the impairment in mitochondrial function after pressure overload, which may then also affect the skeletal muscle. We aimed to characterize changes in mitochondrial function of skeletal muscle during the transition from pressure overload (PO) induced ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535515 Mon, 07 Nov 2011 05:00:00 +0100 5535515 http://www.medworm.com/index.php?rid=5378388&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004457%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378388 Sat, 05 Nov 2011 22:15:49 +0100 5378388 http://www.medworm.com/index.php?rid=5535522&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004639%2Fabstract%3Frss%3Dyes Abstract: Endothelial hyperpermeability followed by edema formation is a hallmark of many severe disorders. Effective drugs directly targeting endothelial barrier function are widely lacking. We hypothesized that the hawthorn (Crataegus spp.) extract WS® 1442, a proven multi-component drug against moderate forms of heart failure, would prevent vascular leakage by affecting endothelial barrier-regulating systems. In vivo, WS® 1442 inhibited the histamine-evoked extravasation of FITC–dextran from mouse cremaster muscle venules. In cultured human endothelial cells, WS® 1442 blocked the thrombin-induced FITC–dextran permeability. By applying biochemical and microscopic techniques, we revealed that WS® 1442 abrogates detrimental effects of thrombin on adherens junctions (vascular endoth... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535522 Wed, 02 Nov 2011 04:00:00 +0100 5535522 http://www.medworm.com/index.php?rid=5626294&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004627%2Fabstract%3Frss%3Dyes The complex functions of cells are controlled by a surprisingly small number of second messengers. Therefore, in order to allow diverse stimuli to produce stimuli-specific cellular outcomes, it is essential that signalling is compartmentalised. In the cardiac myocyte, evidence for this fundamental principle was first presented some 3 decades ago for two of the most universal of second messengers, Ca2+ and cyclic AMP, with the recognition that the dyad was the localised site of Ca2+-induced Ca2+ release , and that β-adrenoceptor (AR) agonists and prostaglandin E1 increase cAMP in distinct cellular compartments, only the former having access to intracellular targets which regulate cardiac contractility . This seminal work has formed the basis for our current understanding of localised signa... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626294 Mon, 31 Oct 2011 04:00:00 +0100 5626294 http://www.medworm.com/index.php?rid=5535531&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004597%2Fabstract%3Frss%3Dyes Abstract: Epac is a guanine nucleotide exchange protein that is directly activated by cAMP, but whose cardiac cellular functions remain unclear. It is important to understand cardiac Epac signaling, because it is activated in parallel to classical cAMP-dependent signaling via protein kinase A. In addition to activating contraction, Ca2+ is a key cardiac transcription regulator (excitation–transcription coupling). It is unknown how myocyte Ca2+ signals are decoded in cardiac myocytes to control nuclear transcription. We examine Epac actions on cytosolic ([Ca2+]i) and intranuclear ([Ca2+]n) Ca2+ homeostasis, focusing on whether Epac alters [Ca2+]n and activates a prohypertrophic program in cardiomyocytes. Adult rat cardiomyocytes, loaded with fluo-3 were viewed by confocal microscopy durin... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535531 Mon, 31 Oct 2011 04:00:00 +0100 5535531 http://www.medworm.com/index.php?rid=5535509&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004615%2Fabstract%3Frss%3Dyes Abstract: The serine–threonine phosphatase calcineurin is activated in cardiac myocytes in the diseased heart and induces pathological hypertrophy. Calcineurin activity is mainly triggered by calcium/calmodulin binding but also through calpain mediated cleavage. How controlled calcineurin activation is possible in cardiac myocytes, which typically show a 10-fold difference in cytosolic calcium concentration with every heartbeat, has remained enigmatic. It is now emerging that calcineurin activation and signaling occur in subcellular microdomains, in which it is brought together with target proteins and exceedingly high concentrations of calcium in order to induce downstream signaling. We review current evidence of subcellular calcineurin mainly at the sarcolemma and the nucleus, but also... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535509 Mon, 31 Oct 2011 04:00:00 +0100 5535509 http://www.medworm.com/index.php?rid=5535501&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100441X%2Fabstract%3Frss%3Dyes In heart cells, membrane potential and intracellular calcium ([Ca2+]i) are closely linked. Each time the heart beats, membrane depolarization opens L-type Ca2+ channels in the cell membrane. Ca2+ entering through these channels triggers the release of a larger amount of Ca2+ via ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR) membrane, a process known as CICR, for Ca2+-induced Ca2+ release. The increase and subsequent decrease in [Ca2+]i, the Ca2+ transient, is the signal that initiates contraction. Conversely, changes in [Ca2+]i can alter membrane potential through Ca2+-dependent ion channels, pumps, and transporters in the cell membrane. Not surprisingly, numerous proteins and pathways are involved in regulating Ca2+ transport in myocytes. When these regulatory systems beco... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535501 Mon, 31 Oct 2011 04:00:00 +0100 5535501 http://www.medworm.com/index.php?rid=5535500&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004603%2Fabstract%3Frss%3Dyes In antiquity, the Roman Empire was known for its technological achievements and innovations that delivered it a contemporary, strategic advantage over neighboring civilizations and played an important role in shaping sequential civilizations, including ours. The Romans were masters in adaptive innovation, revising existing concepts and inventions by earlier empires, most notably the Etruscans, Greeks and Egyptians, by taking them to new and innovative levels of use and functionality. Several Roman technological feats in different areas like civil engineering, construction materials, transport technology, and military technology were surprising achievements until the 19th century, and some, such as the invention of the architectural arch, have remained untouched to this day. A central conce... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535500 Mon, 31 Oct 2011 04:00:00 +0100 5535500 http://www.medworm.com/index.php?rid=5626316&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004421%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Highlights: ► Hypertrophy can be adaptive or pathological. ► Cardiac myocyte-FAK overexpression in mice induced compensated cardiac hypertrophy. ► Upregulation of FAK was accompanied by activation of PI3K, AKT, mTOR, S6K and rpS6. ► Inhibition of the mTOR complex by rapamycin extinguished the cardiac hypertrophy. ► FAK activation may be important for the adaptive responses to increases in cardiac afterload. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626316 Fri, 28 Oct 2011 04:00:00 +0100 5626316 http://www.medworm.com/index.php?rid=5535526&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004408%2Fabstract%3Frss%3Dyes Abstract: The expression of bone morphogenic protein 4 (BMP4), a new pro-inflammatory marker, is increased by disturbed flow in endothelial cells (ECs). BMP4 stimulates production of reactive oxygen species (ROS) and causes endothelial cell dysfunction. The present study examined BMP4-induced apoptosis in ECs and isolated arteries from rat, mouse, and human, and the signaling pathways mediating BMP4-induced apoptosis. Apoptosis was assessed by flow cytometry to detect Annexin-V positive cells, and terminal deoxynucleotidyl transferase dUTP nick end (TUNEL) labeling. The superoxide production was measured by dihydroethidium fluorescence. BMP4 induced EC apoptosis in human mesenteric arteries, mouse aortic endothelium, rat primary ECs, and human ECs. BMP4-induced EC apoptosis was mediated th... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535526 Fri, 28 Oct 2011 04:00:00 +0100 5535526 http://www.medworm.com/index.php?rid=5535513&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004366%2Fabstract%3Frss%3Dyes Abstract: Clinical trials infusing Bone Marrow Cells (BMCs) into injured hearts have produced measureable improvements in cardiac performance, but were insufficient to improve patient outcomes. Low engraftment rates are cited as probable contributor to limited improvements. To understand the mechanisms that control myocardial engraftment of BMCs following ischemia-reperfusion injury, in isolated–perfused mouse hearts, stop-flow ischemia was followed by variable-duration reperfusion (0–60min) before addition of labeled syngenic BMCs to the perfusate. After a buffer-only wash, the heart was disaggregated. Retained BMCs (digest) and infused BMCs (aliquot) were compared by flow cytometry for c-kit and CD45 expression to determine the proportion of cell subtypes engrafted versus delivered (... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535513 Fri, 28 Oct 2011 04:00:00 +0100 5535513 http://www.medworm.com/index.php?rid=5535529&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004391%2Fabstract%3Frss%3Dyes In conclusion, we demonstrate a differentially regulated cohort of microRNAs that predicts differences in cellular proliferation in CPCs during postnatal development and target microRNAs that are involved in this transition. Our study provides new insights that may enhance the utilization of adult CPCs for regenerative therapy of the injured myocardium.Highlights: ► MicroRNA profiles in cardiac progenitor cells (CPCs) are distinct developmentally. ► The predicted protein targets are predominantly involved in cellular proliferation. ► The proliferative capacity of neonatal CPCs is higher than adult CPCs. ► Over-expression of miR-17-92 increases the proliferation in adult CPCs. ► A cohort of microRNAs may predict differences in cellular proliferation in CPCs. (Source: Journal of Mo... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535529 Mon, 24 Oct 2011 04:00:00 +0100 5535529 http://www.medworm.com/index.php?rid=5535512&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100438X%2Fabstract%3Frss%3Dyes Abstract: While ethanol intake at high levels (3–4 or more drinks), either in acute (occasional binge drinking) or chronic (daily) settings, increases the risk for myocardial infarction and stroke, an inverse relationship between regular consumption of alcoholic beverages at light to moderate levels (1–2 drinks per day) and cardiovascular risk has been consistently noted in a large number of epidemiologic studies. Although initially attributed to polyphenolic antioxidants in red wine, subsequent work has established that the ethanol component contributes to the beneficial effects associated with moderate intake of alcoholic beverages regardless of type (red versus white wine, beer, spirits). Concerns have been raised with regard to interpretation of epidemiologic evidence for this asso... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535512 Mon, 24 Oct 2011 04:00:00 +0100 5535512 http://www.medworm.com/index.php?rid=5535502&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004330%2Fabstract%3Frss%3Dyes Hearts of women and men are not the same—there is an expanding literature which attests to sex difference in normal cardiac electromechanical function and structure . In women, ventricular mass and chamber size is smaller , heart rate is higher with longer QT interval , and although ejection fraction is usually greater at rest it is less robustly increased with exercise in women than men . There is also growing evidence that cardiac pathophysiology evolves differently in women and men. Premenopausally, women have lower cardiac risk, but in the event of a myocardial infarct they experience higher mortality and rate of heart failure . From observational studies a strong case for ovarian steroid cardioprotection can be made—yet two large clinical trials failed to identify benefit of hormo... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535502 Thu, 20 Oct 2011 04:00:00 +0100 5535502 http://www.medworm.com/index.php?rid=5535520&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004354%2Fabstract%3Frss%3Dyes Abstract: Inhibition of tumor suppressor p53 is cardioprotective against ischemic injury and provides resistance to subsequent cardiac remodeling. We investigated p53-mediated expansion of ischemic damage with a focus on mitochondrial integrity in association with autophagy and apoptosis. p53−/− heart showed that autophagic flux was promoted under ischemia without a change in cardiac tissue ATP content. Electron micrographs revealed that ischemic border zone in p53−/− mice had 5-fold greater numbers of autophagic vacuoles containing mitochondria, indicating the occurrence of mitophagy, with an apparent reduction of abnormal mitochondria compared with those in WT mice. Analysis of autophagic mediators acting downstream of p53 revealed that TIGAR (TP53-induced glycolysis and apoptosi... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535520 Tue, 18 Oct 2011 04:00:00 +0100 5535520 http://www.medworm.com/index.php?rid=5535528&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004329%2Fabstract%3Frss%3Dyes Abstract: Initial clinical studies indicate a potential beneficial effect of erythropoietin (EPO) in patients with anemia and heart failure. Here, we investigate the direct contractile effects of erythropoietin on myocardial tissue. Treatment with EPO (50U/mL) using excitable murine and human left ventricular muscle preparations resulted in a 37% and 62% increase in twitch tension, respectively (P (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535528 Mon, 17 Oct 2011 04:00:00 +0100 5535528 http://www.medworm.com/index.php?rid=5535503&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004317%2Fabstract%3Frss%3Dyes Myocardial infarction (MI), a mostly local restriction of blood supply (ischemia) to the heart muscle by occlusion of a coronary artery, results in damage or, if left untreated for an extended time period, in death of a large number of cardiomyocytes. Necrosis, in turn, triggers an inflammation process that helps to eliminate dead cells and defective extracellular matrix in the affected region. In fish and amphibia remaining cardiomyocytes can re-enter the cell-cycle and divide again, fully regenerating lost or damaged pieces of the heart . Adult mammals are less fortunate as their cardiomyocytes remain locked in the G0 phase of the cell cycle. They help themselves with generating a fibrous tissue scar that is beneficial as a means to stabilize the wound and restrict the damage, but cannot... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535503 Mon, 17 Oct 2011 04:00:00 +0100 5535503 http://www.medworm.com/index.php?rid=5535517&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004299%2Fabstract%3Frss%3Dyes The objective of this study was to investigate the nature and biomechanical properties of collagen fibers within the human myocardium. Targeting cardiac interstitial abnormalities will likely become a major focus of future preventative strategies with regard to the management of cardiac dysfunction. Current knowledge regarding the component structures of myocardial collagen networks is limited, further delineation of which will require application of more innovative technologies. We applied a novel methodology involving combined confocal laser scanning and atomic force microscopy to investigate myocardial collagen within ex-vivo right atrial tissue from 10 patients undergoing elective coronary bypass surgery. Immuno-fluorescent co-staining revealed discrete collagen I and III fibers. Durin... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535517 Wed, 12 Oct 2011 04:00:00 +0100 5535517 http://www.medworm.com/index.php?rid=5535523&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004263%2Fabstract%3Frss%3Dyes Abstract: Both the sympathetic nervous system and the proinflammatory cytokine interleukin-18 (IL-18) play key roles in the pathophysiology of the hypertrophied failing heart. IL-18 binding protein (IL-18BP), a natural inhibitor of IL-18, counters its biological effects. β-AR stimulation induces IL-18 expression, but whether it also regulates IL-18BP is not known. Here we demonstrate that the β-AR agonist isoproterenol (ISO) increases steady state IL-18BP mRNA and protein levels in adult mouse cardiomyocytes in a β2-AR-dependent manner. We cloned mouse Il18bp 5′cis-regulatory region, and identified putative CREB and C/EBPβ transcription factor-binding sites. Forced expression of mutant CREB or C/EBPβ knockdown markedly attenuated ISO-induced Il18bp transcription and deletion or muta... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535523 Mon, 10 Oct 2011 04:00:00 +0100 5535523 http://www.medworm.com/index.php?rid=5378390&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004275%2Fabstract%3Frss%3Dyes As recently reviewed in a special issue of this Journal , heart failure is a major clinical cause of morbidity and mortality. Advances in therapies for heart failure have improved patient outcomes substantially over the past 30years ; but unfortunately, the pace of these advances has slowed considerably in recent years, with few new therapies becoming available recently . Thus, there is a real need for new therapies and new targets for the treatment of heart failure . (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378390 Mon, 10 Oct 2011 04:00:00 +0100 5378390 http://www.medworm.com/index.php?rid=5271210&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004081%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271210 Sun, 02 Oct 2011 04:50:41 +0100 5271210 http://www.medworm.com/index.php?rid=5271180&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003907%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271180 Sun, 02 Oct 2011 04:50:36 +0100 5271180 http://www.medworm.com/index.php?rid=5535521&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004251%2Fabstract%3Frss%3Dyes In this study, alanine mutants of hERG S6 and pore helix residues and MthK-based homology modelling and ligand docking were used to investigate molecular determinants of DISO binding to hERG. Whole-cell hERG current (IhERG) recordings were made at 37°C from HEK-293 cells expressing WT or mutant hERG channels. WT outward IhERG tails were inhibited with an IC50 of 7.3μM, whilst inward IhERG tails in a high [K+]e of 94mM were blocked with an IC50 of 25.7μM. The IC50 for the Y652A mutation was ~55-fold that of WT IhERG; this mutation also abolished a leftward shift in voltage-dependent IhERG activation present for WT hERG. The IC50 for F656A IhERG was ~51 fold its corresponding WT control. In contrast to previously studied methanesulphonanilide hERG inhibitors, neither the G648A S6 nor the ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535521 Wed, 28 Sep 2011 04:00:00 +0100 5535521 http://www.medworm.com/index.php?rid=5535505&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100424X%2Fabstract%3Frss%3Dyes In this study, Casq2 knockout mice (Casq2−/−) were used as a model to evaluate the effects of the Casq2 on the cytosolic and intra-SR Ca2+ dynamics, and the electrical activity in the ventricular epicardial layer of intact beating hearts. Casq2−/− mice have accelerated intra-SR Ca2+ refilling kinetics (76±22 vs. 136.5±15ms) and a reduced refractoriness of Ca2+ release (182±32ms Casq2+/+ and 111±22ms Casq2−/− ). In addition, mice display reduced Ca2+ alternans (67% decline in the amplitude of Ca2+ alternans at 7 Hz, 21oC) and less T-wave alternans at the electrocardiographic level. The results presented in this paper support the idea of Casq2 acting both as a buffer and a direct regulator of the Ca2+ release process. Finally, we propose that alterations in Ca2+ release refra... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535505 Wed, 28 Sep 2011 04:00:00 +0100 5535505 http://www.medworm.com/index.php?rid=5626312&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004202%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Highlights: ► Cardiomyopathies are associated with metabolic stress, oxidative stress, and arrhythmic risk. ► Oxidative stress alters ion channels, Ca2+ handling, and gap junctions, possibly explaining the arrhythmic risk. ► Anti-oxidants may be useful anti-arrhythmic drugs. ► Highlights ROS mediate arrhythmogenesis through the alteration of ion homeostasis and structural remodeling. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626312 Mon, 26 Sep 2011 04:00:00 +0100 5626312 http://www.medworm.com/index.php?rid=5535524&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004214%2Fabstract%3Frss%3Dyes Abstract: Cardiac myosin binding protein-C (cMyBP-C) has 11 immunoglobulin or fibronectin-like domains, C0 through C10, which bind sarcomeric proteins, including titin, myosin and actin. Using bacterial expressed mouse N-terminal fragments (C0 through C3) in an in vitro motility assay of myosin-generated actin movement and the laser trap assay to assess single molecule actin-binding capacity, we determined that the first N-terminal 17 amino acids of the cMyBP-C motif (the linker between C1 and C2) contain a strong, stereospecific actin-binding site that depends on positive charge due to a cluster of arginines. Phosphorylation of 4 serines within the motif decreases the fragments' actin-binding capacity and actomyosin inhibition. Using the laser trap assay, we observed individual cMyBP-C fr... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535524 Mon, 26 Sep 2011 04:00:00 +0100 5535524 http://www.medworm.com/index.php?rid=5535511&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004147%2Fabstract%3Frss%3Dyes Abstract: Statins are widely used in the treatment of dyslipidemia and associated cardiovascular abnormalities including atherosclerosis, hypertension and coronary heart disease. Needless to mention, statins have cholesterol-lowering effects by means of inhibiting 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, a rate-limiting enzyme of cholesterol biosynthesis. Besides cholesterol-lowering effects, statins possess pleiotropic anti-inflammatory, anti-oxidant, anti-platelet and anti-fibrotic properties, which may additionally play imperative roles in statins-mediated cardiovascular protection. However, the precise mechanisms involved in the cardiovascular defensive potential of statins have not completely been elucidated. Intriguingly, a considerable number of studies demonstrated the p... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535511 Mon, 26 Sep 2011 04:00:00 +0100 5535511 http://www.medworm.com/index.php?rid=5535510&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004159%2Fabstract%3Frss%3Dyes We describe different models of microRNA-based regulation of gene expression. ► We review how single microRNAs regulate pathological cardiac remodeling. ► We provide an overview of microRNA target genes in cardiac hypertrophic growth. ► We divide microRNAs into either pro- or anti-hypertrophic properties. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535510 Mon, 26 Sep 2011 04:00:00 +0100 5535510 http://www.medworm.com/index.php?rid=5535508&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004123%2Fabstract%3Frss%3Dyes Abstract: Mitochondria are involved in cellular functions that go beyond the traditional role of these organelles as the power plants of the cell. Mitochondria have been implicated in several human diseases, including cardiac dysfunction, and play a role in the aging process. Many aspects of our knowledge of mitochondria stem from studies performed on the isolated organelle. Their relative inaccessibility imposes experimental difficulties to study mitochondria in their natural environment—the cytosol of intact cells—and has hampered a comprehensive understanding of the plethora of mitochondrial functions. Here we review currently available methods to study mitochondrial function in intact cardiomyocytes. These methods primarily use different flavors of fluorescent dyes and genetically ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535508 Mon, 26 Sep 2011 04:00:00 +0100 5535508 http://www.medworm.com/index.php?rid=5378407&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004135%2Fabstract%3Frss%3Dyes Abstract: Heart failure is associated with a change in cardiac energy metabolism. SIRT1 is a NAD+-dependent protein deacetylase, and important in the regulation of cellular energy metabolism. To examine the role of SIRT1 in cardiac energy metabolism, we created transgenic mice overexpressing SIRT1 in a cardiac-specific manner, and investigated cardiac functional reserve, energy reserve, substrate uptake, and markers of mitochondrial function. High overexpression of SIRT1 caused dilated cardiomyopathy. Moderate overexpression of SIRT1 impaired cardiac diastolic function, but did not cause heart failure. Fatty acid uptake was decreased and the number of degenerated mitochondria was increased dependent on SIRT1 gene dosage. Markers of reactive oxygen species were decreased. Changes in morphol... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378407 Mon, 26 Sep 2011 04:00:00 +0100 5378407 http://www.medworm.com/index.php?rid=5378403&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004160%2Fabstract%3Frss%3Dyes Abstract: Earlier investigations in our lab indicated an anti-adrenergic effect induced by activation of p21-activated kinase (Pak-1) and protein phosphatase 2A (PP2A). Our objective was to test the hypothesis that Pak-1/PP2A is a signaling cascade controlling stress-induced cardiac growth. We determined the effects of ablation of the Pak-1 gene on the response of the myocardium to chronic stress of isoproterenol (ISO) administration. Wild-type (WT) and Pak-1-knockout (Pak-1-KO) mice were randomized into six groups to receive either ISO, saline (CTRL), or ISO and FR180204, a selective inhibitor of Erk1/2. Echocardiography revealed that hearts of the Pak-1-KO/ISO group had increased LV fractional shortening, reduced LV chamber volume in diastole and systole, increased cardiac hypertrophy, a... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378403 Mon, 26 Sep 2011 04:00:00 +0100 5378403 http://www.medworm.com/index.php?rid=5378395&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811004111%2Fabstract%3Frss%3Dyes Abstract: E2Fs are a family of transcription factors that regulate proliferation, differentiation and apoptosis in many cell types. E2F-1 is the prototypical E2F and the family member that has most often been implicated in also mediating apoptosis. To better understand the role of E2F-1 in mediating cardiomyocyte injury we initially analyzed E2F family member expression after ischemia/reperfusion (I/R) in vivo or simulated ischemia in vitro. I/R injury in vivo caused a 3.4-fold increase specifically in E2F-1 protein levels. Expression of other E2F family members did not change. To establish the role of E2F-1 in I/R we examined the response of germline deleted E2F-1 mice to I/R injury. Infarct size as a percentage of the area at risk was decreased 39.8% in E2F-1−/− mice compared to E2F-... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378395 Fri, 23 Sep 2011 04:00:00 +0100 5378395 http://www.medworm.com/index.php?rid=5535518&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003877%2Fabstract%3Frss%3Dyes Abstract: Cardiac myosin binding protein-C (cMyBP-C) is a thick filament assembly protein that stabilizes sarcomeric structure and regulates cardiac function; however, the profile of cMyBP-C degradation after myocardial infarction (MI) is unknown. We hypothesized that cMyBP-C is sensitive to proteolysis and is specifically increased in the bloodstream post-MI in rats and humans. Under these circumstances, elevated levels of degraded cMyBP-C could be used as a diagnostic tool to confirm MI. To test this hypothesis, we first established that cMyBP-C dephosphorylation is directly associated with increased degradation of this myofilament protein, leading to its release in vitro. Using neonatal rat ventricular cardiomyocytes in vitro, we were able to correlate the induction of hypoxic stress wi... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535518 Wed, 21 Sep 2011 04:00:00 +0100 5535518 http://www.medworm.com/index.php?rid=5626314&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003841%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Graphical abstract: Highlights: ► Vascular smooth muscle cells synthesize and secrete adiponectin. ► VSMC-derived adiponectin is upregulated by PPARγ agonists. ► VSMC-derived adiponectin is required for contractile protein expression. ► VSMC-derived adiponectin acts in an autocrine and paracrine fashion. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626314 Mon, 19 Sep 2011 04:00:00 +0100 5626314 http://www.medworm.com/index.php?rid=5626311&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100383X%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Highlights: ► Role of mitochondria in myocardial ischemia–reperfusion injury. ► Mitochondrial adenine nucleotide transport in ischemia–reperfusion injury. ► Role of voltage dependent anion channel (VDAC) in mitochondrial ATP transport. ► Mitochondrial ATP transport and mitochondrial permeability transition pore (mPTP). (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626311 Mon, 19 Sep 2011 04:00:00 +0100 5626311 http://www.medworm.com/index.php?rid=5626301&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003828%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Highlights: ► Different from plasmalemmal eNOS, sarcoplasmic nNOS facilitates basal myocardial relaxation and attenuates contraction. ► nNOS promotes PKA-dependent phospholamban phosphorylation and inhibits L-type Ca2+ channel activity. ► nNOS modulates myocardial oxidases and maintains eNOS ‘coupling’ to produce NO. ► nNOS is up-regulated and translocates to sarcolemma in diseased heart and attenuates its adverse remodeling. ► eNOS is ‘uncoupled’ and contributes to oxidative stress in failing myocardium. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626301 Mon, 19 Sep 2011 04:00:00 +0100 5626301 http://www.medworm.com/index.php?rid=5220817&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003452%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5220817 Thu, 15 Sep 2011 16:35:03 +0100 5220817 http://www.medworm.com/index.php?rid=5378404&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003816%2Fabstract%3Frss%3Dyes Abstract: HCN pacemaker channels (If channels) are believed to contribute to important functions in the heart; thus these channels became an attractive target for generating transgenic mouse mutants to elucidate their role in physiological and pathophysiological cardiac conditions. A full understanding of cardiac If and the interpretation of studies using HCN mouse mutants require detailed information about the expression profile of the individual HCN subunits. Here we investigate the cardiac expression pattern of the HCN isoforms at the mRNA as well as at the protein level. The specificity of antibodies used was strictly confirmed by the use of HCN1, HCN2 and HCN4 knockout animals. We find a low, but highly differential HCN expression profile outside the cardiac conduction pathway includi... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378404 Thu, 15 Sep 2011 04:00:00 +0100 5378404 http://www.medworm.com/index.php?rid=5378393&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003804%2Fabstract%3Frss%3Dyes Abstract: Whether intracellular Ca2+ regulates sinoatrial node cell (SANC) action potential (AP) firing rate on a beat-to-beat basis is controversial. To directly test the hypothesis of beat-to-beat intracellular Ca2+ regulation of the rate and rhythm of SANC we loaded single isolated SANC with a caged Ca2+ buffer, NP-EGTA, and simultaneously recorded membrane potential and intracellular Ca2+. Prior to introduction of the caged Ca2+ buffer, spontaneous local Ca2+ releases (LCRs) during diastolic depolarization were tightly coupled to rhythmic APs (r2=0.9). The buffer markedly prolonged the decay time (T50) and moderately reduced the amplitude of the AP-induced Ca2+ transient and partially depleted the SR load, suppressed spontaneous diastolic LCRs and uncoupled them from AP generation, and... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378393 Thu, 15 Sep 2011 04:00:00 +0100 5378393 http://www.medworm.com/index.php?rid=5535506&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003774%2Fabstract%3Frss%3Dyes This study compared Ca2+ homeostasis in ventricular myocytes from 8-month-old female C57BL/6J mice that had either a bilateral ovariectomy (OVX) or a sham surgery at 3weeks of age. Cells were loaded with fura-2 and field-stimulated or voltage-clamped with steps to membrane potentials between −40 and +80mV (37°C). Peak Ca2+ transients increased by two-fold in OVX myocytes when compared to sham, and Ca2+ transient rates of rise and decay were faster in OVX cells. In contrast, Ca2+ current densities were similar in sham and OVX cells. Sarcoplasmic reticulum (SR) Ca2+ content, assessed by caffeine, also was higher in OVX compared to sham cells (111.7±11.9 vs. 61.2±10.4nM; p (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535506 Wed, 14 Sep 2011 04:00:00 +0100 5535506 http://www.medworm.com/index.php?rid=5378396&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003786%2Fabstract%3Frss%3Dyes Abstract: Modulation of purinergic signaling is critical to myocardial homeostasis. Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD-1; CD39) which converts the proinflammatory molecules ATP or ADP to AMP is a key regulator of purinergic modulation. However, the salutary effects of transgenic over expression of ENTPD-1 on myocardial response to ischemic injury have not been tested to date. Therefore we hypothesized that ENTPD-1 over expression affords myocardial protection from ischemia–reperfusion injury via specific cell signaling pathways. ENTPD-1 transgenic mice, which over express human ENTPDase-1, and wild-type (WT) littermates were subjected to either ex vivo or in vivo ischemia–reperfusion injury. Infarct size, inflammatory cell infiltrate and intracellular signaling mol... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378396 Wed, 14 Sep 2011 04:00:00 +0100 5378396 http://www.medworm.com/index.php?rid=5378389&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003798%2Fabstract%3Frss%3Dyes The integrity of mitochondrial function is pivotal to cell and organ homeostasis. Emerging evidence is rapidly enhancing our understanding of the myriad of programs controlling mitochondrial health, turnover and repair. These processes include the exclusion of impaired fragments of mitochondria via fission and fusion (mitochondrial dynamics) , the recycling of de-energized mitochondrial via mitophagy , and the replication or expansion of mitochondria via the mitochondrial biogenesis program . Whether all of these programs are uniformly active and how they are coordinated in different tissues that are either; i) intrinsically rapidly dividing (hemopoietic precursor cells) or not (e.g. the heart and brain); ii) have divergent bioenergetic demands and/or iii) distinct mitochondrial functions ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378389 Wed, 14 Sep 2011 04:00:00 +0100 5378389 http://www.medworm.com/index.php?rid=5535514&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003762%2Fabstract%3Frss%3Dyes Abstract: In cardiac myocytes, cytochalasin D (CytoD) was reported to act as an actin disruptor and mechanical uncoupler. Using confocal and super-resolution STED microscopy, we show that CytoD preserves the actin filament architecture of adult rat ventricular myocytes in culture. Five hundred nanomolar CytoD was the optimal concentration to achieve both preservation of the T-tubular structure during culture periods of 3days and conservation of major functional characteristics such as action potentials, calcium transients and, importantly, the contractile properties of single myocytes. Therefore, we conclude that the addition of CytoD to the culture of adult cardiac myocytes can indeed be used to generate a solid single-cell model that preserves both morphology and function of freshly isol... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535514 Mon, 12 Sep 2011 04:00:00 +0100 5535514 http://www.medworm.com/index.php?rid=5378402&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003725%2Fabstract%3Frss%3Dyes In conclusion, our data using an in vivo model of cardiac dysfunction (late-phase hypertrophy), suggest that βIIPKC contributes to the pathology associated with heart failure and thus an inhibitor of βIIPKC may be a potential treatment for this disease.Highlights: ►Selective βIIPKC inhibition improves cardiac function and survival in heart failure. ►βIIPKC inhibition reverses pathological cardiac remodeling. ►βIIV5-3 peptide suppresses myocardial fibrosis and inflammation. ►βIIPKC inhibition improves calcium handling and myocardial contractility. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378402 Mon, 05 Sep 2011 04:00:00 +0100 5378402 http://www.medworm.com/index.php?rid=5378401&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003713%2Fabstract%3Frss%3Dyes This study aims to investigate the use of UTE MRI to detect fibrosis after myocardial infarction without using exogenous contrast. In 7 male Lewis rats either myocardial infarction was created (n=5) or sham surgery was performed (n=2). Six weeks after surgery, hearts were isolated and visualized by MRI. Images were acquired with UTE (TE 0.15ms), to detect tissue with a fast T2* decay. Acquired conventional images (TE=6.0ms) were subtracted from UTE images to maintain only ‘short living signal’ (SLS): tissue with a fast decay. In infarcted hearts, SLS was observed in subtracted images, whereas in control hearts hardly any SLS was detected. Subtracted images were cross-referenced with histology and showed that the SLS area observed with UTE MRI corresponded to the collagen-rich areas obs... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378401 Mon, 05 Sep 2011 04:00:00 +0100 5378401 http://www.medworm.com/index.php?rid=5378392&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003737%2Fabstract%3Frss%3Dyes This article is part of a Special issue entitled "Possible Editorial".Highlights: ► dATP enhances myocardial contraction via increased crossbridge binding and kinetics. ► [dATP] can be increased >10-fold via ribonucleotide reductase (Rrm) overxpression. ► Rrm overexpression increased intact cardiomyocyte contractility and relaxation. ► Rrm overexpression had no effect on Ca2+ transient magnitude. ► Myofilament targeted gene manipulations can improve cardiac function. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378392 Mon, 05 Sep 2011 04:00:00 +0100 5378392 http://www.medworm.com/index.php?rid=5378398&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003701%2Fabstract%3Frss%3Dyes Abstract: Whether adenosine, a crucial regulator of the developing cardiovascular system, can provoke arrhythmias in the embryonic/fetal heart remains controversial. Here, we aimed to establish a mechanistic basis of how an adenosinergic stimulation alters function of the developing heart. Spontaneously beating hearts or dissected atria and ventricle obtained from 4-day-old chick embryos were exposed to adenosine or specific agonists of the receptors A1AR (CCPA), A2AAR (CGS-21680) and A3AR (IB-MECA). Expression of the receptors was determined by quantitative PCR. The functional consequences of blockade of NADPH oxidase, extracellular signal-regulated kinase (ERK), phospholipase C (PLC), protein kinase C (PKC) and L-type calcium channel (LCC) in combination with adenosine or CCPA, were inve... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378398 Fri, 02 Sep 2011 04:00:00 +0100 5378398 http://www.medworm.com/index.php?rid=5535507&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003403%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled ‘Possible Editorial’.Highlights: ► Unlike TB4 treatment prior to MI, TB4 treatment after MI does not reprogram epicardial cells into cardiomyocytes. ► Epicardial cells treated with TB4 after MI adopt mesenchymal fibroblast fate. ► TB4 stimulates epicardial cells proliferation in vivo. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535507 Mon, 29 Aug 2011 04:00:00 +0100 5535507 http://www.medworm.com/index.php?rid=5378400&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003427%2Fabstract%3Frss%3Dyes Abstract: We have demonstrated that the natural flavone acacetin selectively inhibits ultra-rapid delayed rectifier potassium current (IKur) in human atria. However, molecular determinants of this ion channel blocker are unknown. The present study was designed to investigate the molecular determinants underlying the ability of acacetin to block hKv1.5 channels (coding IKur) in human atrial myocytes using the whole-cell patch voltage-clamp technique to record membrane current in HEK 293 cells stably expressing the hKv1.5 gene or transiently expressing mutant hKv1.5 genes generated by site-directed mutagenesis. It was found that acacetin blocked hKv1.5 channels by binding to both closed and open channels. The blockade of hKv1.5 channels by acacetin was use- and frequency-dependent, and the I... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378400 Mon, 29 Aug 2011 04:00:00 +0100 5378400 http://www.medworm.com/index.php?rid=5626313&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100335X%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Highlights: ► We determined an interaction between S100B and vascular endothelial growth factor. ► In rat cardiocyte cultures, S100B increased VEGF mRNA, protein, and secretion. ► In culture, rat cardiac fibroblasts undergo phenotypic transition to myofibroblasts. ► VEGF induces via VEGFR-2, ERK1/2 phosphorylation and myofibroblast proliferation. ► Myofibroblast proliferation contributes to scar formation in infarcted myocardium. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626313 Thu, 25 Aug 2011 04:00:00 +0100 5626313 http://www.medworm.com/index.php?rid=5626308&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003336%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Graphical abstract: Highlights: ► During metabolic impairment, a change in the ATP:ADP ratio stimulates KATP channels opening. ► The ATP:AMP ratio is an acquisitively sensitive indicator of alterations in the metabolic status. ► We show that AMP-activated protein kinase (AMPK) activity promotes KATP channel opening. ► AMPK physically interacts with KATP channel subunits, suggestive of local signaling. ► Thus, small changes in AMP may trigger KATP channel availability under ischemic conditions. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626308 Thu, 25 Aug 2011 04:00:00 +0100 5626308 http://www.medworm.com/index.php?rid=5626305&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003348%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Highlights: ► L-type Ca2+ channels regulate diverse cellular processes in the heart. ► Different L-type Ca2+ channel subpopulations exist in cardiomyocytes. ► Function and regulation of L-type Ca2+ channels depend on subcellular localization. ► Altered localization of L-type Ca2+ channels plays a role in heart disease. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626305 Thu, 25 Aug 2011 04:00:00 +0100 5626305 http://www.medworm.com/index.php?rid=5626299&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003361%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes.”Highlights: ► Intracellular cAMP is not uniformly distributed within cardiomyocytes. ► Cyclic AMP microdomains confer specificity of the response to various hormones. ► Degradation of cAMP by phosphodiesterases is critical for the formation of cAMP microdomains. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626299 Thu, 25 Aug 2011 04:00:00 +0100 5626299 http://www.medworm.com/index.php?rid=5271186&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003373%2Fabstract%3Frss%3Dyes Abstract: MicroRNAs (miRNAs) are strong post-transcriptional regulators targeting multiple targets. Endogenously transcribed, miRNAs specifically bind to complementary sequences of mRNAs and repress their expression thus govern control of cellular signaling pathways. An altered miRNA expression is causally related to cardiovascular disease. Identification of miRNA-dependent pathways is therefore an important aim to develop new therapeutic approaches. To understand miRNA function in various cardiovascular cells, the identification of individual miRNA target genes is of utmost importance. Indeed, the biological function of a miRNA is dependent on the availability of potential targets in a cell. We here summarize and discuss current challenging approaches to identify miRNA targetomes which wi... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271186 Thu, 25 Aug 2011 04:00:00 +0100 5271186 http://www.medworm.com/index.php?rid=5378406&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003324%2Fabstract%3Frss%3Dyes In conclusion, MMP 2 and 9 activation is essential for CCG and is mediated, in part, by p38 MAPK. Furthermore, compromised CCG in the metabolic syndrome may be partially due to the lack of p38 MAPK-dependent activation of MMP 2 and 9 and resultant decreased extracellular matrix degradation.Highlights: ► p38 MAPK is required for MMP 2/9 activity during coronary collateral growth (CG). ► MMP 2/9 activity is essential for extracellular matrix (ECM) degradation and CG. ► Lack of CG in metabolic syndrome correlates with lack of MMP 2/9 activity and reduced ECM degradation. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378406 Mon, 22 Aug 2011 04:00:00 +0100 5378406 http://www.medworm.com/index.php?rid=5378397&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003300%2Fabstract%3Frss%3Dyes Abstract: To explore whether CaMKII-dependent phosphorylation events mediate reperfusion arrhythmias, Langendorff perfused hearts were submitted to global ischemia/reperfusion. Epicardial monophasic or transmembrane action potentials and contractility were recorded. In rat hearts, reperfusion significantly increased the number of premature beats (PBs) relative to pre-ischemic values. This arrhythmic pattern was associated with a significant increase in CaMKII-dependent phosphorylation of Ser2814 on Ca2+-release channels (RyR2) and Thr17 on phospholamban (PLN) at the sarcoplasmic reticulum (SR). These phenomena could be prevented by the CaMKII-inhibitor KN-93. In transgenic mice with targeted inhibition of CaMKII at the SR membranes (SR-AIP), PBs were significantly decreased from 31±6 to 5... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378397 Mon, 22 Aug 2011 04:00:00 +0100 5378397 http://www.medworm.com/index.php?rid=5271199&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003312%2Fabstract%3Frss%3Dyes Abstract: We previously demonstrated that syntaxin (Syn)-1A is present in the sarcolemma of rat cardiomyocytes and binds sulfonylurea receptor (SUR) 2A nucleotide binding folds (NBFs) to inhibit ATP-sensitive potassium (KATP) channel. Here, we examined for the precise domains within the NBFs of SUR2A that may interact with Syn-1A. Specifically, we tested truncated NBF protein segments encompassing the conserved motifs Walker A (WA), signature/Linker (L), and Walker B (WB). In vitro binding results indicate that the domains encompassing WA and L of NBF-1 and all three conserved motifs of NBF-2 bound Syn-1A. Electrophysiological studies, employing inside-out patch-clamp recordings from SUR2A/Kir6.2 expressing HEK cells and mouse cardiomyocytes, show that WB and L of NBF-1 and all three NBF-2... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271199 Mon, 22 Aug 2011 04:00:00 +0100 5271199 http://www.medworm.com/index.php?rid=5378405&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003282%2Fabstract%3Frss%3Dyes Abstract: Low-dose oral tetrahydrocannabinol (THC) reduces progression of atherosclerosis in mice. THC activates central cannabinoid-1 receptors (CB1) with subsequent psychoactive effects as well as peripheral cannabinoid-2 receptors (CB2). In order to dissect the underlying mechanisms, we performed experiments under selective CB2 stimulation as well as after genetic disruption of the CB2 receptor. Atherosclerosis prone apolipoprotein E-deficient mice were crossed with cannabinoid receptor-2 deficient mice to obtain ApoE −/− CB2 −/− double knockout mice. After 8weeks of a high-cholesterol diet, immunohistochemical stainings of the aortic root revealed that vascular leukocyte infiltration in atherosclerotic plaques was accelerated in ApoE −/− CB2 −/− mice compared with ApoE ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378405 Fri, 19 Aug 2011 04:00:00 +0100 5378405 http://www.medworm.com/index.php?rid=5271187&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003270%2Fabstract%3Frss%3Dyes Abstract: In the neonatal mammalian heart, the role of ryanodine receptor (=Ca2+ release channel)-mediated sarcoplasmic reticulum (SR) Ca2+ release for excitation–contraction coupling is still a matter of debate. Using an adenoviral system, we overexpressed separately the junctional SR proteins triadin, junctin, and calsequestrin, which are probably involved in regulation of ryanodine receptor function. Infection of neonatal rat cardiac myocytes with triadin, junctin, or calsequestrin viruses, controlled by green fluorescent protein expression, resulted in an increased protein level of the corresponding transgenes. Measurement of Ca2+ transients of infected cardiac myocytes revealed unchanged peak amplitudes under basal conditions but with overexpression of calsequestrin and triadin caff... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271187 Thu, 18 Aug 2011 04:00:00 +0100 5271187 http://www.medworm.com/index.php?rid=5378399&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003245%2Fabstract%3Frss%3Dyes Abstract: Advances in understanding of the maintenance of the cardiac valves during normal cardiac function and response to injury have led to several novel findings, including that there is contribution of extra-cardiac cells to the major cellular population of the valve: the valve interstitial cell (VIC). While suggested to occur in human heart studies, we have been able to experimentally demonstrate, using a mouse model, that cells of bone marrow hematopoietic stem cell origin engraft into the valves and synthesize collagen type I. Based on these initial findings, we sought to further characterize this cell population in terms of its similarity to VICs and begin to elucidate its contribution to valve homeostasis. To accomplish this, chimeric mice whose bone marrow was repopulated with e... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378399 Wed, 17 Aug 2011 04:00:00 +0100 5378399 http://www.medworm.com/index.php?rid=5378394&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003191%2Fabstract%3Frss%3Dyes Abstract: Type 2 diabetes is associated with an increased risk of cardiac complications. Inhibitors of dipeptidylpeptidase 4 (DPP-4) are novel drugs for the treatment of patients with type 2 diabetes. The effect of DPP-4 inhibitors on myocardial metabolism has not been studied in detail. In wild-type C57Bl6-mice, 3weeks of treatment with sitagliptin had no effect on body weight and glucose tolerance nor on phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoAcarboxylase (ACC), phosphofructokinase-2 (PFK2) or tuberin-2 (TSC2) in the left ventricular myocardium. However, in 10week old db/db−/− mice, a model of diabetes and obesity, sitagliptin potently reduced plasma glucose rise in peritoneal glucose tolerance tests and reduced weight increase. The myocardium of untreate... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378394 Tue, 16 Aug 2011 04:00:00 +0100 5378394 http://www.medworm.com/index.php?rid=5271181&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100321X%2Fabstract%3Frss%3Dyes The importance of [Ca2+] in the mitochondrial matrix, [Ca2+]mito , had been proposed by early work of Carafoli and others . The key suggestion in the 1970s was that regulatory [Ca2+]mito played a role in controlling the rate of activation of tricarboxylic acid cycle dehydrogenases, important in the regulation of ATP production by the electron transport chain (ETC) during oxidative phosphorylation. This view is now established and the key questions currently debated are to what extent do the mitochondria acquire and release Ca2+, and what impact do mitochondria have on the dynamic Ca2+ signal in the cardiac ventricular myocyte . Although investigations of Ca2+ dynamics in mitochondria have been problematic, disparate and inconclusive, they have also been both provocative and exciting. A rec... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271181 Tue, 16 Aug 2011 04:00:00 +0100 5271181 http://www.medworm.com/index.php?rid=5220823&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003208%2Fabstract%3Frss%3Dyes In 2001, the Mochly-Rosen laboratory published the first evidence that inhibition of delta protein kinase C (δPKC) at the onset of reperfusion reduced tissue injury in preclinical models of acute myocardial infarction (AMI). In various models of cardiac ischemia and reperfusion (I/R) including cultured neonatal cardiac myocytes , ex vivo whole rat heart , and in vivo porcine heart , we demonstrated that delivering a rationally designed peptide allosteric inhibitor of δPKC (δV1-1) at reperfusion reduced infarct size by about 70% . δV1-1 treatment reduced necrosis and apoptosis, accelerated ATP regeneration, preserved mitochondrial structure, and preserved organization of contractile elements . We also found that treatment with δV1-1 protected the vascular endothelium, leading to improv... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5220823 Tue, 16 Aug 2011 04:00:00 +0100 5220823 http://www.medworm.com/index.php?rid=5220821&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003221%2Fabstract%3Frss%3Dyes The past three decades have witnessed a significant decrease in the age-adjusted incidence of coronary artery disease (CAD), the primary cause of cardiovascular (CV) death, due largely to the widespread adoption of cholesterol-lowering medications. Heart failure is the second leading cause of CV death, and is steadily increasing, with approximately 12.5million people currently diagnosed with heart failure and nearly one million lives lost each year . The economic burden of this problem is similarly substantial: heart failure accounts for 10% of total worldwide cardiovascular healthcare costs, approximately $55billion dollars annually, with hospital care representing more than 80% of the cost burden . Despite the need for efficacious therapies for heart failure, there is relatively little d... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5220821 Tue, 16 Aug 2011 04:00:00 +0100 5220821 http://www.medworm.com/index.php?rid=5220818&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003233%2Fabstract%3Frss%3Dyes This special issue of JMCC contains focused reviews on 25 key cardiac signaling molecules or processes that are potential drug targets to treat heart failure (HF) (), plus an original article on one of those molecules. There are also 5 editorials describing the promise and pitfalls in developing new drugs for HF, from a HF clinical trialist ; leaders at the NHLBI ; the head of cardiovascular discovery at Merck ; experts in the science of translational research ; and an accomplished basic scientist who has taken a novel drug into clinical trials . The issue includes a paper illustrating new HF drug development from concept to clinic , and a review showing how cell and drug therapy are complimentary . (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5220818 Tue, 16 Aug 2011 04:00:00 +0100 5220818 http://www.medworm.com/index.php?rid=5626310&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003154%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled ‘‘Local Signaling in Myocytes’’.Highlights: ► The role of mitochondrial tubulin beta II and its role in respiration regulation are described. ► Mitochondrial tubulin beta II is rapidly removed by short proteolytic treatment of permeabilized cardiomyocytes. ► Removal of tubulin increases the permeability of outer mitochondrial membrane for ADP. ► Quality tests for isolated cardiomyocytes are described. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626310 Mon, 08 Aug 2011 04:00:00 +0100 5626310 http://www.medworm.com/index.php?rid=5626300&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003178%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes.”Highlights: ► cGMP is an important intracellular second messenger in cardiac myocytes. ► cGMP signaling specificity through compartmentalization of synthesis and hydrolysis. ► cGMP signals cross-talk with cAMP signals through phosphodiesterases. ► cGMP-dependent signaling pathways inhibit cardiac remodeling. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626300 Mon, 08 Aug 2011 04:00:00 +0100 5626300 http://www.medworm.com/index.php?rid=5271202&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100318X%2Fabstract%3Frss%3Dyes Abstract: Heat shock transcription factor 1 (HSF1) plays an important role not only in excise-induced cardiac hypertrophy but also in protection against pressure overload-induced cardiac dysfunction. However, the mechanism is not completely understood. We here elucidate the potential mechanisms by which HSF1 protects against pressure overload-induced cardiac remodeling and dysfunction. A sustained constriction of transverse aorta (TAC) was imposed to HSF1 transgenic (TG), knockout (KO) and their littermate wild type (WT) male mice. Four weeks later, adaptive responses to TAC, such as cardiac hypertrophy, contractility and angiogenesis evaluated by echocardiography, catheterization, coronary perfusion pressure and immunohistochemistry were well preserved in TG but not in KO compared with WT... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271202 Mon, 08 Aug 2011 04:00:00 +0100 5271202 http://www.medworm.com/index.php?rid=5271201&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003142%2Fabstract%3Frss%3Dyes In this study, we sought to permanently alter calcium fluxes via phospholamban (PLN) gene deletion in Tm180 mice in order to sustain long-term improvements in cardiac function and adverse cardiac remodeling/hypertrophy. While similar work has been done in FHCs resulting from mutations in thick myofilament proteins, no one has studied these effects in an FHC resulting from a thin filament protein mutation. Tm180 transgenic (TG) mice were crossbred with PLN knockout (KO) mice and four groups were studied in parallel: 1) non-TG (NTG), 2) Tm180, 3) PLNKO/NTG and 4) PLNKO/Tm180. Tm180 mice exhibit increased heart weight/body weight and hypertrophic gene markers compared to NTG mice, but levels in PLNKO/Tm180 mice were similar to NTG. Tm180 mice also displayed altered function as assessed via in... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271201 Mon, 08 Aug 2011 04:00:00 +0100 5271201 http://www.medworm.com/index.php?rid=5271192&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003166%2Fabstract%3Frss%3Dyes Abstract: Recent perspectives on sinoatrial nodal cell (SANC)⁎ function indicate that spontaneous sarcoplasmic reticulum (SR) Ca2+ cycling, i.e. an intracellular “Ca2+ clock,” driven by cAMP-mediated, PKA-dependent phosphorylation, interacts with an ensemble of surface membrane electrogenic molecules (“surface membrane clock”) to drive SANC normal automaticity. The role of AC-cAMP-PKA-Ca2+ signaling cascade in mouse, the species most often utilized for genetic manipulations, however, has not been systematically tested. Here we show that Ca2+ cycling proteins (e.g. RyR2, NCX1, and SERCA2) are abundantly expressed in mouse SAN and that spontaneous, rhythmic SR generated local Ca2+ releases (LCRs) occur in skinned mouse SANC, clamped at constant physiologic [Ca2+]. Mouse SANC also e... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271192 Mon, 08 Aug 2011 04:00:00 +0100 5271192 http://www.medworm.com/index.php?rid=5378391&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003117%2Fabstract%3Frss%3Dyes Abstract: The mitofusin proteins MFN1 and MFN2 function to maintain mitochondrial networks by binding one another and initiating outer mitochondrial membrane fusion. While it has recently been recognized that vascular endothelial cells rely upon mitochondria as signaling rather than energy-producing moieties, the role of mitochondrial dynamics in endothelial cell function has not been addressed. To begin to understand what role mitochondrial dynamics play in this context, we examined the regulation of MFN1 and MFN2 and the consequences of siRNA-mediated knockdown of these proteins in cultured endothelial cells. Treatment with VEGF-A led to the upregulation of MFN2 and, to a lesser extent, MFN1. Knockdown of either MFN led to disrupted mitochondrial networks and diminished mitochondrial mem... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5378391 Thu, 04 Aug 2011 04:00:00 +0100 5378391 http://www.medworm.com/index.php?rid=5271206&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003129%2Fabstract%3Frss%3Dyes Abstract: In certain cases of endothelial dysfunction l-arginine becomes rate-limiting for NO synthesis in spite of sufficiently high plasma concentrations of the amino acid. To better understand this phenomenon, we investigated routes of substrate supply to endothelial nitric oxide synthase (eNOS). Our previous data with human umbilical vein (HUVEC) and EA.hy.926 endothelial cells demonstrated that eNOS can obtain its substrate from the conversion of l-citrulline to l-arginine and from protein breakdown. In the present study, we determined the quantitative contribution of proteasomal and lysosomal protein degradation and investigated to what extent extracellular peptides and l-citrulline can provide substrate to eNOS. The RFL-6 reporter cell assay was used to measure eNOS activity in huma... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271206 Thu, 04 Aug 2011 04:00:00 +0100 5271206 http://www.medworm.com/index.php?rid=5085854&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002835%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085854 Tue, 02 Aug 2011 08:31:35 +0100 5085854 http://www.medworm.com/index.php?rid=5626317&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003075%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Highlights: ► We show that 5-HT2A receptors/caveolin-3 interaction increases upon agonist exposure. ► 5-HT2A receptors stimulated with 5-HT traffic into caveolae microdomains. ► Caveolin-3 silencing enhances myocyte hypertrophy induced by 5-HT2A receptors. ► Caveolin-3 inhibits NFAT activation involved in 5-HT2A receptor-mediated hypertrophy. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626317 Fri, 29 Jul 2011 04:00:00 +0100 5626317 http://www.medworm.com/index.php?rid=5271209&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003051%2Fabstract%3Frss%3Dyes Abstract: HIV-infected patients have a high prevalence of long QT syndrome (LQTs). hERG K+ channel encoded by human ether-a-go-go related gene contributes to IKr K+ currents responsible for the repolarization of cardiomyocytes. Inhibition of hERG K+ channels leads to LQTs. HIV Tat protein, the virus transactivator protein, plays a pivotal role in AIDS. The aim of the present study is to examine the effects of HIV Tat protein on hERG K+ channels stably expressed in HEK293 cells. The hERG K+ currents were recorded by whole-cell patch-clamp technique and the hERG channel expression was measured by real-time PCR and Western blot techniques. HIV Tat protein at 200ng/ml concentration showed no acute effect on hERG currents, but HIV Tat protein (200ng/ml) incubation for 24h significantly inhibite... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271209 Fri, 29 Jul 2011 04:00:00 +0100 5271209 http://www.medworm.com/index.php?rid=5271207&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003087%2Fabstract%3Frss%3Dyes In conclusion, this study reveals novel insights into the relationship of rosiglitazone and cardiovascular events by providing a model that links rosiglitazone-induced osteoblast-like differentiation, oxidative stress and apoptosis with mineralization in VSMCs. In addition, we position resveratrol in this model acting to reduce rosiglitazone-induced oxidative stress, osteoblast-like VSMC differentiation and mineralization.Highlights: ► We study the regulation of vascular mineralization using a human VSMC in vitro model. ► Rosiglitazone stimulates mineralization partly via caspase-dependent apoptosis. ► Rosiglitazone-induced oxidative stress correlates with osteoblast-like differentiation phenotype. ► Resveratrol reduces osteoblast-like differentiation. ► Resveratrol counteracts t... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271207 Fri, 29 Jul 2011 04:00:00 +0100 5271207 http://www.medworm.com/index.php?rid=5271193&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811003063%2Fabstract%3Frss%3Dyes Conclusions: Feed-forward basal Ca2+-cAMP/PKA signaling both consumes ATP to drive spontaneous APs in SANC and is tightly linked to mitochondrial ATP production. Interfering with Ca2+-cAMP/PKA signaling not only slows the firing rate and reduces ATP consumption, but also appears to reduce ATP production so that ATP levels fall. This distinctly differs from VM, which lack this feed-forward basal cAMP/PKA signaling, and in which ATP level remains constant when the demand changes.Highlights: ► We explored the mechanisms that match ATP supply and demand in pacemaker cells. ► O2 consumption in pacemaker cells is comparable to stimulated ventricular myocytes. ► Reduction in Ca2+-cAMP/PKA signaling in pacemaker cells reduced ATP production. ► Ca2+-cAMP/PKA signaling in pacemaker cells lin... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271193 Fri, 29 Jul 2011 04:00:00 +0100 5271193 http://www.medworm.com/index.php?rid=5271194&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100304X%2Fabstract%3Frss%3Dyes Abstract: Doxorubicin (DOX) is one of the most effective chemotherapeutic agents, but cardiotoxicity limits DOX therapy. Although the mechanisms are not entirely understood, reactive oxygen species (ROS) appear to be involved in DOX cardiotoxicity. Ca/calmodulin dependent protein kinase II (CaMKII) can be activated by ROS through oxidation and is known to contribute to myocardial dysfunction through Ca leakage from the sarcoplasmic reticulum (SR). We hypothesized that CaMKII contributes to DOX-induced defects in intracellular Ca ([Ca]i) handling. Cardiac myocytes were isolated from wild-type (WT) adult rat hearts and from mouse hearts lacking the predominant myocardial CaMKII isoform (CaMKIIδ−/−, KO) vs. WT. Isolated cardiomyocytes were investigated 30min after DOX (10μmol/L) superfu... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271194 Thu, 28 Jul 2011 04:00:00 +0100 5271194 http://www.medworm.com/index.php?rid=5626309&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100280X%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes.”Highlights: ► The mechanism of linear dependence of mitochondrial respiration on heart work is described. ► The role of tubulin and plectin in formation of Intracellular Energetic Units. ► The mitochondrial tubulin beta II and its role in respiration regulation are described. ► Feedback metabolic regulation on beat to beat basis is described. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626309 Wed, 27 Jul 2011 04:00:00 +0100 5626309 http://www.medworm.com/index.php?rid=5271184&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002793%2Fabstract%3Frss%3Dyes Abstract: Ischemic diseases remain one of the major causes of morbidity and mortality throughout the world. In recent clinical trials on cell-based therapies, the use of adult stem and progenitor cells only elicited marginal benefits. Therapeutic neovascularisation is the Holy Grail for ischemic tissue recovery. There is compelling evidence from animal transplantation studies that the inclusion of mural cells in addition to endothelial cells (ECs) can enhance the formation of functional blood vessels. Vascular smooth muscle cells (SMCs) and pericytes are essential for the stabilisation of nascent immature endothelial tubes. Despite the intense interest in the utility of human embryonic stem cells (ESCs) for vascular regenerative medicine, ESC-derived vascular SMCs have received much less a... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271184 Tue, 26 Jul 2011 04:00:00 +0100 5271184 http://www.medworm.com/index.php?rid=5271208&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002768%2Fabstract%3Frss%3Dyes Abstract: Circulating microRNAs may have diagnostic potential in acute coronary syndrome (ACS). Previous studies, however, were based on low patient numbers and could not assess the relation of microRNAs to clinical characteristics and their potential prognostic value. We thus assessed the diagnostic and prognostic value of cardiomyocyte-enriched microRNAs in the context of clinical variables and a sensitive myonecrosis biomarker in a larger ACS cohort. MiR-1, miR-133a, miR-133b, miR-208a, miR-208b, and miR-499 concentrations were measured by quantitative reverse transcription PCR in plasma samples obtained on admission from 444 patients with ACS. High-sensitivity troponin T (hsTnT) was measured by immunoassay. Patients were followed for 6months regarding all-cause mortality. In a multiple... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271208 Mon, 25 Jul 2011 04:00:00 +0100 5271208 http://www.medworm.com/index.php?rid=5271191&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100277X%2Fabstract%3Frss%3Dyes Abstract: The transient outward current Ito is an important determinant of the early repolarization phase. Ito and its molecular basis Kv4.3 are regulated by adrenergic pathways including protein kinase C. However, the exact regulatory mechanisms have not been analyzed yet. We here analyzed isoenzyme specific regulation of Kv4.3 and Ito by PKC. Kv4.3 channels were expressed in Xenopus oocytes and currents were measured with double electrode voltage clamp technique. Patch clamp experiments were performed in isolated rat cardiomyocytes. Unspecific PKC stimulation with PMA resulted in a reduction of Kv4.3 current. Similar effects could be observed after activation of conventional PKC isoforms by TMX. Both effects were reversible by pharmacological inhibition of the conventional PKC isoenzymes... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271191 Mon, 25 Jul 2011 04:00:00 +0100 5271191 http://www.medworm.com/index.php?rid=5271185&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002781%2Fabstract%3Frss%3Dyes Abstract: Protein kinase C (PKC) is a family of 10 serine/threonine kinases divided into 3 subfamilies, classical, novel and atypical classes. Two PKC isozymes of the novel group, PKCε and PKCδ, have different and sometimes opposite effects. PKCε stimulates cell growth and differentiation while PKCδ is apoptotic. In the heart, they are among the most expressed PKC isozymes and they are opposed in the preconditioning process with a positive role of PKCε and an inhibiting role of PKCδ. The goal of this review is to analyze the structural differences of these 2 enzymes that may explain their different behaviors and properties.Highlights: ► PKCε and PKCδ are members of the same family of PKCs. ► They have different and sometimes opposite effects. ► We analyze their structural dif... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271185 Mon, 25 Jul 2011 04:00:00 +0100 5271185 http://www.medworm.com/index.php?rid=5535504&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002756%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled ‘Possible Editorial’.Highlights: ► Here we describe the development of an automated screening assay to determine cardiomyocyte cell size. ► We used this assay to screen 230 miRNAs for their hypertrophy-modulating potential. ► Thereby we identified major hypertrophy-modulating miRNAs. ► Among them are several miRNAs that have previously not been involved in cardiomyocyte biology. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5535504 Thu, 21 Jul 2011 04:00:00 +0100 5535504 http://www.medworm.com/index.php?rid=5626304&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002719%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes.”Highlights: ► Caveolae are protein compartments that control the production of cAMP and NO. ► Some signalling pathways exploit the lipid (PIP2) environment of caveolae. ► Caveolae can buffer increases in membrane tension during stretch. ► Caveolae are key components of GPCR and mechanotransductive signalling in the heart. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626304 Mon, 18 Jul 2011 04:00:00 +0100 5626304 http://www.medworm.com/index.php?rid=5271200&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002744%2Fabstract%3Frss%3Dyes Abstract: Endothelial cells (EC) serve a paracrine function to enhance signaling in cardiomyocytes (CM), and conversely, CM secrete factors that impact EC function. Understanding how EC interact with CM may be critically important in the context of ischemia–reperfusion injury, where EC might promote CM survival. We used isoflurane as a pharmacological stimulus to enhance EC protection of CM against hypoxia and reoxygenation injury. Triggering of intracellular signal transduction pathways culminating in the enhanced production of nitric oxide (NO) appears to be a central component of pharmacologically induced cardioprotection. Although the endothelium is well recognized as a regulator for vascular tone, little attention has been given to its potential importance in mediating cardioprotect... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271200 Mon, 18 Jul 2011 04:00:00 +0100 5271200 http://www.medworm.com/index.php?rid=5271190&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002720%2Fabstract%3Frss%3Dyes In conclusion, CAVB induces two waves of molecular remodeling: an early one (≤24h) leading to arrhythmias, a later one related to hypertrophy. These results provide new molecular basis for ventricular tachycardia induced by AV block.Highlights: ► Novel mouse model of CAVB using a radiofrequency-mediated ablation procedure. ► CAVB induces early (≤24h) spontaneous polymorphic ventricular tachycardia. ► CAVB induces a later structural remodeling and adaptive cardiac hypertrophy. ► New molecular basis at the genome-wide level for ventricular tachycardia. ► Decrease in prominent repolarizing current is central to the electrical remodeling. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271190 Mon, 18 Jul 2011 04:00:00 +0100 5271190 http://www.medworm.com/index.php?rid=5271189&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002707%2Fabstract%3Frss%3Dyes This study aimed to enhance the survival and angiogenic capacity of human umbilical cord blood (UCB)-derived mononuclear cells (MNCs) and to demonstrate their therapeutic effects on experimental ischemia. A specific culture medium containing five growth factors (Flt-3L, EGF, TPO, FGF and IGF-1) augmented cell proliferation, adhesion potential as well as stimulated MNCs to become progenitor-like cells. In addition, qRT-PCR demonstrated that MNCs cultured with these five growth factors (5f-MNCs) markedly up-regulated multiple angiogenic, arteriogenic and anti-apoptotic factors compared with uncultured MNCs. In an ischemic hindlimb model, the injection of 5f-MNCs prevented limb loss and augmented blood perfusion, capillary density, vascular maturation and angiogenic cytokines in the affected ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271189 Mon, 18 Jul 2011 04:00:00 +0100 5271189 http://www.medworm.com/index.php?rid=5271183&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002690%2Fabstract%3Frss%3Dyes We describe their potential advantages and shortcomings compared to existing imaging approaches, and what is needed in terms of validation and characterization before these agents can be exploited clinically.Highlights: ► Molecular imaging of hypoxia is an attractive diagnostic and prognostic approach. ► PET has significant advantages in terms of sensitivity, speed and spatial resolution. ► Misonidazole based agents have poor first pass uptake and slow blood clearance. ► Cu-BTSC complexes are tuneable to different levels of hypoxia and have fast kinetics. ► CuATSM is the only BTSC which has been studied in the heart; more must be screened and validated. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271183 Fri, 15 Jul 2011 04:00:00 +0100 5271183 http://www.medworm.com/index.php?rid=5271205&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002653%2Fabstract%3Frss%3Dyes This study investigated genetic variability in the angiotensin-II type-1 receptor (AGTR1), angiotensin-converting enzyme (ACE), and ACE2 genes as cardiac phenotype modifying factors in FRDA patients. Comprehensive review of the AGTR1, ACE and ACE2 genes identified twelve haplotype tagging SNPs. Correlation of these SNPs with left ventricular internal diameter in diastole (LVIDd), interventricular septal wall thickness (SWT) and left ventricular mass (LVM) was examined in a large Australian FRDA cohort (n=79) with adjustments performed for GAA repeats, age, sex, body surface area and diastolic blood pressure. A significant inverse relationship was observed between GAA1 and LVIDd (p=0.010) but not with SWT or LVM after adjustment for covariates. The AGTR1 polymorphism rs5186 was more common ... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271205 Wed, 13 Jul 2011 04:00:00 +0100 5271205 http://www.medworm.com/index.php?rid=5271197&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002677%2Fabstract%3Frss%3Dyes Abstract: Heat shock protein 60 (HSP60), expressed on the surface of endothelial cells (ECs) stressed by e.g. oxidized LDL or mechanical shear, was shown to function as an auto-antigen and thus as a pro-atherosclerotic molecule. The aim of this study was to determine whether cigarette smoke chemicals can lead to the activation of the “HSP60 pathway.” It was also our aim to elucidate the dynamics of HSP60 from gene expression to endothelial surface expression and secretion. Here we show for the first time that the exposure of human umbilical vein endothelial cells (HUVECs) to cigarette smoke extract (CSE) results in an up-regulation of HSP60 mRNA. Live cell imaging analysis of a HSP60-EYFP fusion protein construct transfected into ECs revealed that mitochondrial structures collapse in r... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271197 Wed, 13 Jul 2011 04:00:00 +0100 5271197 http://www.medworm.com/index.php?rid=5271195&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002665%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled ‘Possible Editorial’.Highlights: ► Permeabilized ventricular myocytes from CPVT mice were used as drug screening assay. ► Potency and efficacy of Ca2+ wave inhibition were analyzed for each drug. ► Flecainide and R-propafenone had highest potency and efficacy of wave inhibition. ► Drug screening assay predicts in vivo antiarrhythmic efficacy in CPVT mice. ► Assay may be useful for testing drug activity against Ca2+ triggered arrhythmias. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271195 Wed, 13 Jul 2011 04:00:00 +0100 5271195 http://www.medworm.com/index.php?rid=5626296&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100263X%2Fabstract%3Frss%3Dyes This article is part of a special issue entitled "Local Signaling in Myocytes."Highlights: ► Changes in sarcoplasmic reticulum (SR) calcium regulate calcium release in heart cells. ► Under many circumstances, regulatory changes in SR calcium are transient and local. ► Studies that established the importance of local changes in SR calcium are described. ► Unresolved and controversial issues requiring further study are discussed. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626296 Mon, 11 Jul 2011 04:00:00 +0100 5626296 http://www.medworm.com/index.php?rid=5271203&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002628%2Fabstract%3Frss%3Dyes Abstract: Cardiac remodeling occurs in the infarcted heart (MI). The underlying regulatory mechanisms are under investigation. Platelet-derived growth factor (PDGF) is a family of growth factors that stimulates cell growth, differentiation and migration. Herein, we sought to determine whether PDGF is involved in cardiac repair/remodeling following MI. The temporal and spatial expressions of PDGF isoforms (A, B, C and D) and PDGF receptor (PDGFR)-α and β as well as cell types expressing PDGF were examined in the infarcted rat heart. Sham-operated rats served as controls. We found that the normal myocardium expressed all PDGF isoforms, and cell types expressing PDGF were primarily interstitial cells. Following MI, PDGF-A and D were significantly increased in the infarcted myocardium during... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271203 Mon, 11 Jul 2011 04:00:00 +0100 5271203 http://www.medworm.com/index.php?rid=5626315&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002604%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Highlights: ► FAK regulates cell adhesion, migration, proliferation and survival. ► The many FAK functions are critical for organismal development and disease. ► Emerging data imply FAK in cardiac development, hypertrophy and failure. ► Therapies to inhibit FAK may prove to be an alternative to treat cardiac diseases. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626315 Mon, 04 Jul 2011 04:00:00 +0100 5626315 http://www.medworm.com/index.php?rid=5271198&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002586%2Fabstract%3Frss%3Dyes The objective of this study was to assess mechanisms of crosstalk between β2-ARs and mitochondrial cell death pathways. DOX administered to WT mice resulted in no acute mortality, however 85% of β2-/- mice died within 30min. Several pro- and anti-survival pathways were altered. The pro-survival kinase, εPKC, was decreased by 64% in β2-/- after DOX vs WT (p (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271198 Mon, 04 Jul 2011 04:00:00 +0100 5271198 http://www.medworm.com/index.php?rid=5271196&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002598%2Fabstract%3Frss%3Dyes In conclusion, our findings identify GIT1 as a new regulator of mitochondrial biogenesis and function, which is necessary for postnatal cardiac maturation.Highlights: ► GIT1 KO mice exhibited cardiac hypertrophy and heart failure. ► Mitochondrial biogenesis was impaired in the hearts of GIT1 KO mice. ► PGC-1α expression was decreased in the hearts of GIT1 KO mice. ► GIT1 KO mice showed decreased mitochondrial function and increased apoptosis. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271196 Mon, 04 Jul 2011 04:00:00 +0100 5271196 http://www.medworm.com/index.php?rid=5271204&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002525%2Fabstract%3Frss%3Dyes In this study, bone marrow-derived mesenchymal stem cells (BMSCs) from Sprague–Dawley rats were infected with lentivirus carrying green fluorescent protein (GFP) gene. The left main coronary arteries of rats were occluded for a 30-min ischemia, followed by a 72h or 28d reperfusion. IPC was induced by 3 cycles of 10s reperfusion and 10s ischemia before sustained reperfusion. GFP–BMSCs were intramyocardially injected at 2h reperfusion. At 70h after transplantation, IPC treatment increased the level of interleukin-10, B-cell leukemia-lymphoma-2 (BCL-2), and vascular endothelial and basic fibroblast growth factor (VEGF and bFGF), and decreased the level of tumor necrosis factor-α, interleukin-1β and BCL-2-associated X protein by ELISA or PCR or western blotting. The BMSCs therapy with IP... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271204 Thu, 30 Jun 2011 04:00:00 +0100 5271204 http://www.medworm.com/index.php?rid=5271188&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002513%2Fabstract%3Frss%3Dyes Abstract: Functioning of the cardiac conduction system depends critically on its structure and its complement of ion channels. Therefore, the aim of this study was to document both the structure and ion channel expression of the left and right ventricular His–Purkinje networks, as we have previously done for the sinoatrial and atrioventricular nodes. A three-dimensional (3D) anatomical computer model of the His–Purkinje network of the rabbit heart was constructed after staining the network by immunoenzyme labelling of a marker protein, middle neurofilament. The bundle of His is a ribbon-like structure and the architecture of the His–Purkinje network differs between the left and right ventricles. The 3D model is able to explain the breakthrough points of the action potential on the ve... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271188 Thu, 30 Jun 2011 04:00:00 +0100 5271188 http://www.medworm.com/index.php?rid=5085870&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002562%2Fabstract%3Frss%3Dyes Abstract: Endothelial nitric oxide synthase (eNOS) has been reported to associate with globular actin, and this association increases eNOS activity. Adenosine, histamine, salbutamol and thrombin cause activation of eNOS through widely different mechanisms. Whether these eNOS agonists can regulate eNOS activity through affecting its association with actin is unknown. As previously reported, we confirmed in cultured human umbilical vein endothelial cells (HUVEC) that histamine and thrombin increased intracellular Ca2+ whereas adenosine and salbutamol did not, and that these four agonists caused different effects on actin filament structure. Nevertheless, despite their divergent effects on intracellular Ca2+ and on actin filament structure, we found by immunoprecipitation that adenosine, hist... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085870 Wed, 29 Jun 2011 23:00:00 +0100 5085870 http://www.medworm.com/index.php?rid=5085867&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002574%2Fabstract%3Frss%3Dyes Abstract: Electrophysiological and pharmacological data from the human heart are limited due to the absence of simple but representative experimental model systems of human myocardium. The aim of this study was to establish and characterise adult human myocardial slices from small patients' heart biopsies as a simple, reproducible and relevant preparation suitable for the study of human cardiac tissue at the multicellular level.Vibratome-cut myocardial slices were prepared from left ventricular biopsies obtained from end-stage heart failure patients undergoing heart transplant or ventricular assist device implantation, and from hearts of normal dogs. Multiple slices were prepared from each biopsy. Regular contractility was observed at a range of stimulation frequencies (0.1–2Hz), and sta... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085867 Wed, 29 Jun 2011 23:00:00 +0100 5085867 http://www.medworm.com/index.php?rid=5220832&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002550%2Fabstract%3Frss%3Dyes This article is part of a special issue entitled “Key Signaling Molecules in Hypertrophy and Heart Failure.”Highlights: ► Neuregulin-1β(Nrg-1β) is a growth and survival factor in the heart and other organs. ► Nrg-1β works in cardiac myocytes via erbB2 and erbB4 receptor tyrosine kinases. ► Nrg-1β/erbB signaling in the heart regulates myocardial adaptation to stress. ► Recombinant Nrg-1β improves heart function in animal models of heart failure (HF). ► Recombinant human Nrg-1β is now being tested in humans as a possible HF therapy. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5220832 Wed, 29 Jun 2011 04:00:00 +0100 5220832 http://www.medworm.com/index.php?rid=4975561&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100232X%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=4975561 Tue, 28 Jun 2011 22:47:41 +0100 4975561 http://www.medworm.com/index.php?rid=5626306&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002537%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Highlights: ► We investigate the mechanism(s) by which caveolae compartmentalise β2-AR signalling. ► Disrupting caveolae reveals β2-AR cAMP signals in the PKA-RII compartment. ► Disrupting caveolae promotes a selective PKA-mediated phosphorylation of PLB. ► Phosphatases (PP) 1/2a (but not PDE 2/3/4) contribute to caveolar β2-AR compartmentation. ► We propose that intact caveolae attenuate cAMP production and limit inhibitory modulation of PP at the SR. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626306 Mon, 27 Jun 2011 04:00:00 +0100 5626306 http://www.medworm.com/index.php?rid=5220846&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002483%2Fabstract%3Frss%3Dyes This article is part of a special issue entitled ‘‘Key Signaling Molecules in Hypertrophy and Heart Failure.’’Highlights: ► Discussion of the role of cardiomyocyte autophagy in cardiac plasticity and disease. ► Therapeutic manipulation of autophagic pathways and governing signaling cascades. ► Autophagy-related patents and putative applications in cardiovascular disease. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5220846 Mon, 27 Jun 2011 04:00:00 +0100 5220846 http://www.medworm.com/index.php?rid=5085865&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002549%2Fabstract%3Frss%3Dyes Abstract: Preconditioning of hearts with the α1-adrenoceptor agonist phenylephrine decreases infarct size and increases the functional recovery of the heart following ischaemia–reperfusion. However, the cellular mechanisms responsible for this protection are not known. We investigated the role of protein kinase C ε and δ (PKCε and PKCδ), AMP-activated protein kinase (AMPK), p38 MAPK (p38) and sarcolemmal ATP-sensitive potassium (sarcKATP) channels in phenylephrine preconditioning using isolated rat ventricular myocytes. Preconditioning of ventricular myocytes with phenylephrine increased the recovery of contractile activity following metabolic inhibition and re-energisation from 30.1±1.9% to 66.5±5.2% (P (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085865 Sun, 26 Jun 2011 23:00:00 +0100 5085865 http://www.medworm.com/index.php?rid=5085857&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002501%2Fabstract%3Frss%3Dyes Abstract: Since techniques for cardiomyocyte isolation were first developed 35years ago, experiments on single myocytes have yielded great insight into their cellular and sub-cellular physiology. These studies have employed a broad range of techniques including electrophysiology, calcium imaging, cell mechanics, immunohistochemistry and protein biochemistry. More recently, techniques for cardiomyocyte culture have gained additional importance with the advent of gene transfer technology. While such studies require a high quality cardiomyocyte population, successful cell isolation and maintenance during culture remain challenging. In this review, we describe methods for the isolation of adult and neonatal ventricular myocytes from rat and mouse heart. This discussion outlines general princip... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085857 Sun, 26 Jun 2011 23:00:00 +0100 5085857 http://www.medworm.com/index.php?rid=5085855&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002495%2Fabstract%3Frss%3Dyes In this issue of the Journal of Molecular and Cellular Cardiology Ren et al. describe a novel culture protocol for cardiomyocyte derivation from human embryonic (hESC) and induced pluripotent stem cells (hiPS). In addition, the utility of fluorescent indicators to monitor calcium and voltage changes in hESC- and hiPS-derived cardiomyocytes and to perform drug screens using optical recordings was suggested. Cardiogenesis was directed by firstly mesodermal specification via the provision of bone-morphogenic-protein 4 (BMP4), followed by cardiomyocyte specification via Wnt-inhibition using two different modes of inhibition. Utilizing this protocol, heterogeneous cell populations containing 16% and 8% cardiomyocytes, for hES and hiPS lines, respectively, were generated. Morphological and funct... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085855 Sun, 26 Jun 2011 23:00:00 +0100 5085855 http://www.medworm.com/index.php?rid=5626307&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002276%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Highlights: ► Transducers and effectors are co-localized for vectorial response to environmental signals. ► Membrane macromolecular units are secluded by diffusion barriers limiting metabolite mobility. ► Membrane complexes comprise local nucleotide sensors able to adjust energy demand. ► Phosphotransfer reactions shunt diffusion barriers and actively modulate nucleotide signals. ► Diffusion barriers permit transmission of only sustained changes in bulk energetics. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626307 Mon, 20 Jun 2011 04:00:00 +0100 5626307 http://www.medworm.com/index.php?rid=5085866&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002288%2Fabstract%3Frss%3Dyes Abstract: The most common clinical tachycardia, Atrial Fibrillation (AF), is a progressive disease, caused by cardiomyocyte remodeling, which finally results in contractile dysfunction and AF persistence. Recently, we identified a protective role of heat shock proteins (HSPs), especially the small HSPB1 member, against tachycardia remodeling in experimental AF models. Our understanding of tachycardia remodeling and anti-remodeling drugs is currently hampered by the lack of suitable (genetic) manipulatable in vivo models for rapid screening of key targets in remodeling. We hypothesized that Drosophila melanogaster can be exploited to study tachycardia remodeling and protective effects of HSPs by drug treatments or by utilizing genetically manipulated small HSP-overexpressing strains. Tachyp... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085866 Sun, 19 Jun 2011 23:00:00 +0100 5085866 http://www.medworm.com/index.php?rid=5085871&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002264%2Fabstract%3Frss%3Dyes Abstract: Viscosity is proposed to modulate diastolic function, but only limited understanding of the source(s) of viscosity exists. In vitro experiments have shown that the proline-glutamic acid–valine–lysine (PEVK) rich element of titin interacts with actin, causing a viscous force in the sarcomere. It is unknown whether this mechanism contributes to viscosity in vivo. We tested the hypothesis that PEVK–actin interaction causes cardiac viscosity and is important in vivo via an integrative physiological study on a unique PEVK knockout (KO) model. Both skinned cardiomyocytes and papillary muscle fibers were isolated from wildtype (WT) and PEVK KO mice and passive viscosity was examined using stretch-hold-release and sinusoidal analysis. Viscosity was reduced by ~60% in KO myocytes an... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085871 Thu, 16 Jun 2011 23:00:00 +0100 5085871 http://www.medworm.com/index.php?rid=5626318&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002239%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Highlights: ► Failing hearts have a severely altered complement of PKA-AKAP signaling nodes. ► Altered PKA-AKAP signaling nodes explain several aspects of the failing phenotype. ► A chemical proteomics strategy reveals aberrant signaling at single AKAP resolution. ► Chemical proteomics identifies novel therapeutic targets for heart failure. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626318 Mon, 13 Jun 2011 04:00:00 +0100 5626318 http://www.medworm.com/index.php?rid=5626297&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002252%2Fabstract%3Frss%3Dyes This article is part of a special issue entitled "Local Signaling in Myocytes."Research highlights: ► Calmodulin (CaM) acts as a local Ca2+ sensor with a limited range of action. ► Ca2+-sensitive ion channels are regulated by dedicated and promiscuous CaMs. ► CaM modulates the sensitivity of CaMKII and calcineurin to local Ca2+ signals. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626297 Mon, 13 Jun 2011 04:00:00 +0100 5626297 http://www.medworm.com/index.php?rid=5085869&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002215%2Fabstract%3Frss%3Dyes Abstract: Distribution of orientations of myosin was examined in ex-vivo myofibrils from hearts of transgenic (Tg) mice expressing Familial Hypertrophic Cardiomyopathy (FHC) troponin T (TnT) mutations I79N, F110I and R278C. Humans are heterozygous for sarcomeric FHC mutations and so hypertrophic myocardium contains a mixture of the wild-type (WT) and mutated (MUT) TnT. If mutations are expressed at a low level there may not be a significant change in the global properties of heart muscle. In contrast, measurements from a few molecules avoid averaging inherent in the global measurements. It is thus important to examine the properties of only a few molecules of muscle. To this end, the lever arm of one out of every 60,000 myosin molecules was labeled with a fluorescent dye and a small volume... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085869 Sun, 12 Jun 2011 23:00:00 +0100 5085869 http://www.medworm.com/index.php?rid=5085868&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002240%2Fabstract%3Frss%3Dyes In conclusions these findings unveil a previously unrecognized function of MSCs in regulating cardiomyocyte proliferation through Notch-1/Jagged-1 pathway and suggest that stromal-myocardial cell juxtacrine and paracrine interactions may contribute to the development of new and more efficient cell-based myocardial repair strategies.Research highlights: ► MSCs are capable of potentiating cardiomyocyte precursor (CSCs) cell proliferation. ► This event involves the activation of Notch-1 signaling. ► MSCs/CSCs interactions may contribute to the development of new myocardial repair strategies. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085868 Sun, 12 Jun 2011 23:00:00 +0100 5085868 http://www.medworm.com/index.php?rid=5085858&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002227%2Fabstract%3Frss%3Dyes Abstract: Acquired cardiovascular diseases such as coronary heart disease, peripheral artery disease and related vascular problems contribute to more than one-third of worldwide morbidity and mortality. In many instances, particularly in the under developed world, cardiovascular diseases are diagnosed at a late stage limiting the scope for improving outcomes. A range of therapies already exist for established cardiovascular disease, although there is significant interest in further understanding disease pathogenesis in order to improve diagnosis and achieve primary and secondary therapeutic goals. The urocortins are a group of recently defined peptide members of the corticotrophin-releasing factor family. Previous pre-clinical work and human association studies suggest that urocortins have... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085858 Sun, 12 Jun 2011 23:00:00 +0100 5085858 http://www.medworm.com/index.php?rid=5085862&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002203%2Fabstract%3Frss%3Dyes In conclusion, we have identified miR-9 as an activation-induced regulator of PDGFR-β expression in cardiomyocytes that is part of a negative feedback loop which serves to modulate PDGFR-β expression upon ligand-stimulation through direct interaction with the 3′UTR of PDFGR-β. This article is part of a Special Issue entitled ‘Possible Editorial’.Research highlights: ► MiR-9 regulates expression of PDGFR-β in cardiomyocytes in a feedback dependent manner. ► Brief exposure of isolated cardiomyocytes or glioblastoma cells to PDGF-BB enhances intracellular levels of miR-9. ► MiR-9 interacts with its predicted seed site in the 3′UTR of PDGFR-β. ► Increasing levels of miR-9 in cardiomyocytes reduces PDGFR-β levels and impairs the angiogenic capacity of cardiomyocytes. ► O... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085862 Sun, 05 Jun 2011 23:00:00 +0100 5085862 http://www.medworm.com/index.php?rid=5271182&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811001878%2Fabstract%3Frss%3Dyes This study examines how mitochondrial energy state dynamically modulates Ca2+ sparks. ► Simultaneous measurements of ΔΨm, ROS, and Ca2+sparks. ► The Ca2+ spark rate is inversely correlated with the energy sate of mitochondria. ► The mechanism involves changes in the local oxidative environment induced by ROS. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5271182 Mon, 30 May 2011 04:00:00 +0100 5271182 http://www.medworm.com/index.php?rid=5220851&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002161%2Fabstract%3Frss%3Dyes This article is part of a special issue entitled “Key Signaling Molecules in Hypertrophy and Heart Failure.”Highlights: ► We review small molecules to activate cardiac regenerative pathways. ► Chemokines may improve stem cell engraftment, survival and differentiation. ► Modulation of genes or cell signaling pathways offers new therapeutic targets. ► Enhancing cell therapy with small molecules will transform cardiac repair potential. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5220851 Mon, 30 May 2011 04:00:00 +0100 5220851 http://www.medworm.com/index.php?rid=5220842&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002185%2Fabstract%3Frss%3Dyes This article is part of a special issue entitled ‘‘Key Signaling Molecules in Hypertrophy and Heart Failure.’’Highlights: ► NOS generates oxidative stress in pressure-overload cardiac hypertrophy. ► This contributes to pathological hypertrophy, fibrosis, and cardiac dysfunction. ► Lower range doses of oral tetrahydrobiopterin (BH4) reverse these changes. ► Higher doses fail. BH4 is oxidized to BH2, fibrosis, and hypertrophy re-appear. ► Defining the therapeutic window for BH4 is key and depends on BH4/BH2 ratio. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5220842 Mon, 30 May 2011 04:00:00 +0100 5220842 http://www.medworm.com/index.php?rid=5085863&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002173%2Fabstract%3Frss%3Dyes We examined effects of activated human blood platelet products on rabbit cardiomyocytes. ► Intracellular Ca2+ increased and action potentials prolonged. ► Early and delayed afterdepolarizations occurred. ► Activated human blood platelets release arrhythmic products. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085863 Sun, 29 May 2011 23:00:00 +0100 5085863 http://www.medworm.com/index.php?rid=5085861&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002197%2Fabstract%3Frss%3Dyes Abstract: Although high intake of n-3 fatty acids is associated with reduced mortality of patients with ischemic heart disease, especially reduction in sudden cardiac death (SCD), the detailed mechanisms remain to be elucidated. Thus, the present study was designed to examine whether long-term treatment with eicosapentaenoic acid (EPA), a major component of n-3 fatty acids, reduces ischemia-induced ventricular fibrillation (VF) in pigs in vivo, and if so, what molecular mechanisms are involved. Male pigs were treated with either a control chow (control group) or a control chow plus EPA (600mg/kg/day, PO, EPA group) for 3weeks and were subjected to myocardial ischemia for 90min (n=8 each) with measurement of the monophasic action potential (MAP), as a marker of ventricular electrophysiologi... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085861 Sun, 29 May 2011 23:00:00 +0100 5085861 http://www.medworm.com/index.php?rid=4871867&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811001921%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=4871867 Sat, 28 May 2011 02:50:35 +0100 4871867 http://www.medworm.com/index.php?rid=5626303&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002148%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled “Local Signaling in Myocytes”.Research highlights: ► The protective and deleterious effects of carbon monoxide (CO) in the myocardium are considered. ► Endogenous CO is clearly protective against ischemia/reperfusion injury. ► Protective effects of CO likely involve multiple second messenger pathways and ion channels. ► At higher concentrations, CO is cardiotoxic and pro-arrhythmic. ► The pro-arrhythmic effects of CO are likely to involve regulation of alternative ion channels. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626303 Fri, 27 May 2011 04:00:00 +0100 5626303 http://www.medworm.com/index.php?rid=4975572&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100215X%2Fabstract%3Frss%3Dyes This study explored metabolic adaptations to expression of the fetal, slow skeletal muscle troponin I (ssTnI). Hearts expressing ssTnI exhibited no significant ATP loss during 5min of global ischemia, while non-transgenic littermates (NTG) showed continual ATP loss. At 7min ischemia TG-ssTnI hearts retained 80±12% of ATP versus 49±6% in NTG (P (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=4975572 Wed, 25 May 2011 23:00:00 +0100 4975572 http://www.medworm.com/index.php?rid=5085860&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002112%2Fabstract%3Frss%3Dyes Abstract: Clinical use of the antineoplastic agent doxorubicin (DOX) is limited by its cardiomyocyte toxicity. Attempts to decrease cardiomyocyte injury showed promising results in vitro, but failed to reduce the adverse effects of DOX in vivo, suggesting that other mechanisms contribute to its cardiotoxicity as well. Evidence that DOX also induces cardiac injury by compromising extracellular matrix integrity is lacking. The matricellular protein thrombospondin-2 (TSP-2) is known for its matrix-preserving function, and for modulating cellular function. Here, we investigated whether TSP-2 modulates the process of doxorubicin-induced cardiomyopathy (DOX-CMP). TSP-2-knockout (TSP-2-KO) and wild-type (WT) mice were treated with DOX (2mg/kg/week) for 12weeks to induce DOX-CMP. Mortality was sig... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085860 Tue, 24 May 2011 23:00:00 +0100 5085860 http://www.medworm.com/index.php?rid=4975565&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002136%2Fabstract%3Frss%3Dyes Conclusions: In a model of MS, the β-blockers metoprolol and nebivolol improve to the same extent LV hemodynamics, remodeling and diastolic function, but nebivolol prevent more markedly endothelium dependent vasorelaxation involving a more marked enhancement of NO bio-availability.Research highlights: ► β-blockade improves of left ventricular diastolic and coronary dysfunctions in rats with metabolic syndrome. ► Enhanced NO bio-availability is involved in the improvement of LV diastolic dysfunction by β-blockers. ► Both coronary endothelial and LV diastolic dysfunctions observed in metabolic syndrome are improved by β-blockade. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=4975565 Tue, 24 May 2011 23:00:00 +0100 4975565 http://www.medworm.com/index.php?rid=4975562&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811002124%2Fabstract%3Frss%3Dyes During the last two decades, the prevalence of obesity has reached epidemic proportions worldwide, leading to the development of a multitude of comorbidities, including hypertension, diabetes mellitus and cardiovascular diseases . Adipose tissue produces and secretes a wide array of adipokines, which have key roles in situ (within the adipose tissue), and as circulating bioactive factors, suggesting that adipose tissue is an essential endocrine organ, in addition to an energy storage depot that modulates fat mass and nutrient homeostasis . Numerous hormones, growth factors and cytokines belong to the adipokine group, including tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor type 1 (PAI-1), leptin, adiponectin and the recently identified resistin . Secreted adipokines sig... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=4975562 Tue, 24 May 2011 23:00:00 +0100 4975562 http://www.medworm.com/index.php?rid=5085864&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811001891%2Fabstract%3Frss%3Dyes Abstract: Tetracaine is a tertiary amine local anaesthetic which inhibits ryanodine receptors (RyRs), the calcium release channels of the sarcoplasmic reticulum (SR). Tetracaine has been extensively used to study the role of the SR Ca2+ fluxes in muscle cells, yet a detailed understanding of tetracaine action on RyR channels is lacking. Here we investigate tetracaine effects in single channel recording of sheep cardiac RyRs in lipid bilayers. Tetracaine decreased channel conductance (block) and open probability (inhibition). The IC50 for inhibition had complex dependencies on membrane voltage and cytoplasmic [ATP], [Ca2+] and pH. We identify three mechanisms underlying these actions. First, a voltage-dependent, slow inhibition in which luminal and cytoplasmic tetracaine compete for a commo... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5085864 Thu, 19 May 2011 23:00:00 +0100 5085864 http://www.medworm.com/index.php?rid=4975568&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100188X%2Fabstract%3Frss%3Dyes Abstract: Our previous study demonstrated that multiple ion channels were heterogeneously expressed in human cardiac fibroblasts, including a large-conductance Ca2+-activated K+ current (BKCa), a volume-sensitive chloride current (ICl.vol), and voltage-gated sodium currents (INa). The present study was designed to examine the possible involvement of these ion channels in proliferation of cultured human cardiac fibroblasts using approaches of cell proliferation assay, whole-cell patch voltage-clamp, siRNA and Western blot analysis. It was found that the blockade of BKCa with paxilline (1–3μM) or ICl.vol with 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid disodium (DIDS, 100–200μM), but not INa with tetrodotoxin (0.1–10μM), remarkably suppressed proliferation in human cardia... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=4975568 Thu, 19 May 2011 23:00:00 +0100 4975568 http://www.medworm.com/index.php?rid=5626302&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811001817%2Fabstract%3Frss%3Dyes This article is part of a Special Issue entitled "Local Signaling in Myocytes".Research highlights: ► In this review, we discuss A-kinase anchoring proteins expressed in the heart. ► AKAPs are important for cAMP compartmentation. ► AKAP scaffold proteins confer specificity and fidelity to cAMP signaling. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626302 Thu, 19 May 2011 04:00:00 +0100 5626302 http://www.medworm.com/index.php?rid=5626298&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811001805%2Fabstract%3Frss%3Dyes This article is part of a special issue entitled “Local Signaling in Myocytes.”Research highlights: ► How myocytes differentiate between contractile and reactive signaling Ca2+ remains a mystery. ► We hypothesize three possibilities and discuss recent work that supports each scenario. ► We present a model in which microdomain Ca2+ and elevated diastolic Ca2+ mobilize reactive cardiac signaling. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626298 Thu, 19 May 2011 04:00:00 +0100 5626298 http://www.medworm.com/index.php?rid=4975566&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811001866%2Fabstract%3Frss%3Dyes This study aims to clarify whether the anti-inflammatory potency of MCPIP contribute to amelioration of septic myocardial inflammation and dysfunction in vivo. Transgenic mice (TG) with cardiac-specific expression of MCPIP and their littermate wild-type (WT) controls were challenged with Escherichia coli LPS (10mg/kg ip) and myocardial function was assessed 18h later using echocardiography. LPS administration markedly deteriorated myocardial contractile function evidenced by reduction of the percentage of left ventricular fractional shortening, which was significantly attenuated by myocardial expression of MCPIP. MCPIP TG mice exhibited a markedly reduced myocardial inflammatory cytokines, less of iNOS expression and peroxynitrite formation, decreased caspase-3/7 activities and apoptotic c... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=4975566 Wed, 18 May 2011 23:00:00 +0100 4975566 http://www.medworm.com/index.php?rid=5220824&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811001854%2Fabstract%3Frss%3Dyes This article is part of a special issue entitled “Key Signaling Molecules in Hypertrophy and Heart Failure.”Highlights: ► Decreased cardiac contractility is a central feature of systolic heart failure. ► Existing drugs that indirectly increase cardiac contractility are limited by mechanism-related adverse effects. ► Direct activation of the sarcomere might improve cardiac performance while avoiding the adverse effects of indirect mechanisms. ► Omecamtiv mecarbil, an allosteric activator of cardiac myosin, was developed to test this hypothesis. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5220824 Wed, 18 May 2011 04:00:00 +0100 5220824 http://www.medworm.com/index.php?rid=4975576&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811001842%2Fabstract%3Frss%3Dyes Abstract: Increasing evidence suggests that local renin–angiotensin system (RAS) plays an important role in cardiac diseases. Elevated p90 ribosomal S6 kinase (RSK) activity has been observed in diabetic animal, as well as in human failing hearts. We hypothesize that RSK mediates cardiac dysfunction by up regulating local RAS signaling. In the present study, we show that the prorenin mRNA level was significantly increased (~5.6-fold) in transgenic mouse hearts with cardiac specific expression of RSK (RSK-Tg). The RSK-Tg mice were more vulnerable to ischemia/reperfusion (I/R) injury than non-transgenic littermate controls (NLC). To further understand the direct contribution of cardiac renin to I/R injury, we used a Langendorff system to evaluate the effect of renin inhibition by aliskiren... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=4975576 Sun, 15 May 2011 23:00:00 +0100 4975576 http://www.medworm.com/index.php?rid=4975573&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811001829%2Fabstract%3Frss%3Dyes In conclusion, exogenous administration of clinical grade AAT reduces caspase-1 activity in the ischemic myocardium leading to preservation of viable myocardium and prevention of adverse cardiac remodeling.Research Highlights: ► Alpha 1 anti trypsin is a naturally occurring anti-inflammatory protein inhibiting caspase-1. ► Alpha 1 anti trypsin blunts ischemia–reperfusion driven caspase-1 activation. ► Alpha 1 anti trypsin prevents cell death during acute myocardial infarction. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=4975573 Sun, 15 May 2011 23:00:00 +0100 4975573 http://www.medworm.com/index.php?rid=4975571&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811001830%2Fabstract%3Frss%3Dyes Abstract: Recently it was shown that lipopolysaccharide (LPS) impairs the pacemaker current in human atrial myocytes. It was speculated that reduced heart rate variability (HRV), typical of patients with severe sepsis, may partially be explained by this impairment. We evaluated the effect of various types of LPS on the activity of human hyperpolarization-activated cyclic nucleotide-gated channel 2 (hHCN2) expressed in HEK293 cells, and on pacemaker channels in native murine sino-atrial node (SAN) cells, in order to determine the structure of LPS necessary to modulate pacemaker channel function. Application of LPS caused a robust inhibition of hHCN2-mediated current (IhHCN2) owing to a negative shift of the voltage dependence of current activation and to a reduced maximal conductance. In ad... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=4975571 Sun, 15 May 2011 23:00:00 +0100 4975571 http://www.medworm.com/index.php?rid=5626295&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS002228281100174X%2Fabstract%3Frss%3Dyes This article is part of a special issue entitled "Local Signaling in Myocytes."Research highlights: ► The background to the development of local control (LC) theories for cardiac excitation–contraction coupling is described. ► LC theories solve the problem of uncontrolled cell-wide regeneration during calcium-induced calcium release (CICR). ► Evidence for LC of CICR includes cytoplasmic Ca sparks and local sarcoplasmic reticulum (SR) calcium depletions (‘blinks’). ► Termination of local CICR remains unclear and key processes contributing to stochastic attrition are discussed. ► Ryanodine receptor gating modulates mean SR Ca levels which may regulate other cellular functions beyond contractility. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=5626295 Tue, 10 May 2011 04:00:00 +0100 5626295 http://www.medworm.com/index.php?rid=4802098&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811001362%2Fabstract%3Frss%3Dyes The Journal of Molecular and Cellular Cardiology is proud to introduce a new publication initiative: The JMCC Methodological Reviews. This review series will provide a new resource for the experimental design and interpretation of key techniques in the fields of cardiovascular animal physiology, cell biology, imaging, electrophysiology, biochemistry, and molecular biology. The feature is intended to provide the JMCC audience open access to the minds and notebooks of “key and trusted” experts in each field. (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=4802098 Tue, 10 May 2011 02:37:20 +0100 4802098 http://www.medworm.com/index.php?rid=4802095&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811001398%2Fabstract%3Frss%3Dyes (Source: Journal of Molecular and Cellular Cardiology) Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=4802095 Tue, 10 May 2011 02:37:19 +0100 4802095 http://www.medworm.com/index.php?rid=4975575&cid=s_38518_171_f&fid=38518&url=http%3A%2F%2Fwww.jmmc-online.com%2Farticle%2FPIIS0022282811001751%2Fabstract%3Frss%3Dyes Abstract: Multiple health benefits of calorie restriction (CR) and alternate day fasting (ADF) regimens are widely recognized. Experimental data concerning the effects of calorie restriction on cardiac health are more controversial, ranging from evidence that ADF protects heart from ischemic damage but results in developing of diastolic dysfunction, to reports that CR ameliorates the age-associated diastolic dysfunction. Here we investigated the effects of chronic CR on morphology and function of the cardiovascular system of aged rats and cardioprotective effect of CR against ischemic damage in the experimental rat model of MI. Cardiovascular fitness of 24-month old Fisher 344 rats maintained through life on ad libitum (AL) or CR diets was extensively evaluated via echocardiography, dobuta... Journal of Molecular and Cellular Cardiology journals http://www.medworm.com/rss/comments.php?id=4975575 Mon, 09 May 2011 23:00:00 +0100 4975575