Basic Research in Cardiology
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Inhibition of the p38 MAP kinase in vivo improves number and functional activity of vasculogenic cells and reduces atherosclerotic disease progression
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In conclusion, this study demonstrates that systemic
p38 MAP kinase inhibition with SB203580 improves the number and function of vasculogenic cells in an animal model of hypercholesterolemia,
and reduces atherosclerotic disease progression in ApoE−/− mice.
Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-009-0072-9Authors
Florian H. Seeger, Universität Frankfurt Institute for Cardiovascular Regeneration, Centre of Molecular Medicine Haus 25, 4. Stock, Theodor-Stern-Kai 7 60590 Frankfurt GermanyDaniel Sedding, University of Giessen and Marburg GmbH Department of Internal Medicine/Card...
Source: Basic Research in Cardiology - November 12, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Peroxisome proliferator-activated receptor-γ activation attenuates cardiac fibrosis in type 2 diabetic rats: the effect of rosiglitazone on myocardial expression of receptor for advanced glycation end products and of connective tissue growth factor
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This study investigated the effects of the PPAR-γ agonist, rosiglitazone, on myocardial expression of
RAGE and CTGF, extent of cardiac fibrosis, and left ventricular (LV) diastolic function in type 2 diabetic (T2D) rats. Twenty-week-old
T2D rats were randomized to treatment with either 20 weeks of rosiglitazone (20 mg/kg) or saline (n = 10 in each group). Serial echocardiographic examinations were performed just before randomization (20 weeks) and at study
completion (40 weeks). Fibrosis extent and RAGE and CTGF expression were assessed in previously imaged hearts by picrosirius
red stain...
Source: Basic Research in Cardiology - November 10, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Depressed expression of MuRF1 and MAFbx in areas remote of recent myocardial infarction: a mechanism contributing to myocardial remodeling?
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Abstract Ventricular remodeling following myocardial infarction (MI) includes myocardial hypertrophy, a process requiring increased
protein synthesis and sarcomere assembly. The anti-hypertrophic effect of MuRF1/MafBx, both muscle-specific E3-ubiquitin ligases,
has been demonstrated in animal experiments and in cultured cardiomyocytes. We assessed MuRF1/MAFbx expression in myocardium
remote of recently (<2 weeks) infarcted regions (MI), compared with patients undergoing coronary artery bypass surgery, with
normal systolic function and without previous infarction (control or Con). Left ventricular myo...
Source: Basic Research in Cardiology - October 26, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Postconditioning with levosimendan reduces the infarct size involving the PI3K pathway and KATP-channel activation but is independent of PDE-III inhibition
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In conclusion, levosimendan applied prior to reperfusion
in acute myocardial infarction significantly reduces the infarct size in an in vivo rat model. This protection involves the
PI3K pathway and the activation of mitochondrial KATP-channels, but is independent of PDE-III inhibition. This finding may
open new possibilities for the treatment of patients with acute myocardial infarction using levosimendan, which is an already
established therapy in cardiogenic shock. Whether the reduction of mortality in cardiogenic shock by levosimendan may in part
be based on this postconditoning effect remains to be elucidated in c...
Source: Basic Research in Cardiology - October 20, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Endothelin-B receptors and ventricular arrhythmogenesis in the rat model of acute myocardial infarction
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We examined the pathophysiologic role of ETB-receptors on ventricular tachyarrhythmias (VT/VF) during myocardial infarction
(MI). MI was induced by coronary ligation in two animal groups, namely in wild-type (n = 63) and in ETB-receptor-deficient (n = 61) rats. Using a telemetry recorder, VT/VF episodes were evaluated during phase I (the 1st hour) and phase II (2–24 h)
post-MI, with and without prior β-blockade. Action potential duration at 90% repolarization (APD90) was measured from monophasic
epicardial recordings and indices of sympathetic activation were assessed using fast-Fourier analy...
Source: Basic Research in Cardiology - October 17, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Mesenchymal stem cell-based prostacyclin synthase gene therapy for pulmonary hypertension rats
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In conclusion, the gene-engineered MSCs would be a suitable cell vector
for gene delivery specifically to the PH lung. The allogeneic PCS-MSC transplantation attenuated PH and cardiovascular remodeling,
and improved the prognosis in PH rats. The MSC-based PCS gene therapy may be a promising strategy for PH treatment.
Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-009-0065-8Authors
Kiyoko Takemiya, Kurume University School of Medicine Department of Internal Medicine Division of Cardio-Vascular Medicine 67 Asahimachi Kurume 830-0011 JapanHisashi Kai, Kurume University School of Medicine D...
Source: Basic Research in Cardiology - October 16, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Role of autoimmunity in dilated cardiomyopathy
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Content Type Journal ArticleCategory EditorialDOI 10.1007/s00395-009-0069-4Authors
Ziya Kaya, University of Heidelberg Department of Cardiology 69120 Heidelberg GermanyHugo A. Katus, University of Heidelberg Department of Cardiology 69120 Heidelberg Germany
Journal Basic Research in CardiologyOnline ISSN 1435-1803Print ISSN 0300-8428 (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - October 14, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Blockade of NF-κB by pyrrolidine dithiocarbamate attenuates myocardial inflammatory response and ventricular dysfunction following coronary microembolization induced by homologous microthrombi in rats
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The objective of this study was to evaluate the effects of specific NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) on
inflammatory response and cardiac function in a rat model of coronary microembolization (CME). CME was developed by injecting
a suspension of microthrombotic particles (MTPs) into the left ventricle when obstructing the ascending aorta. MTPs were generated
from the rat clots sized by filtration through 38 μm screen. Thirty-two Sprague–Dawley rats served as sham group, 128 CME
rats were randomized to untreated (CMEU) and PDTC-treated (CMEp) group. Rats in CMEp were administered intraperitone...
Source: Basic Research in Cardiology - October 13, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Adrenomedullin is increased in alveolar macrophages and released from the lungs into the circulation in severe heart failure
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Abstract Adrenomedullin (AM) is a potent vasorelaxing peptide with natriuretic, diuretic, and growth inhibitory properties. Plasma
concentrations and myocardial AM expression are increased in heart failure (HF). Since AM and AM binding sites are abundantly
expressed in the lungs, we investigated to what extent pulmonary AM and AM receptor subtypes [CRLR/RAMP2 (AM1) and CRLR/RAMP3 (AM2)] are changed in HF and whether the lungs contribute to the increased plasma concentrations of AM reported in HF. Pulmonary
AM mRNA and protein expression were increased by 2.8- and 2.6-fold, respectively, whereas mRNA expressio...
Source: Basic Research in Cardiology - October 13, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
PDGF-CC induces tissue factor expression: role of PDGF receptor α/β
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This study
assesses the impact of PDGF-CC on TF expression in human cells. PDGF-CC concentration-dependently induced TF expression by
2.5-fold in THP-1 cells, by 2.0-fold in human peripheral blood monocytes, by 1.4-fold in vascular smooth muscle cells, and
by 2.6-fold in microvascular endothelial cells, but did not affect TF expression in aortic endothelial cells. A similar pattern
was observed with PDGF-BB. In contrast, PDGF-AA did not alter TF expression in THP-1 cells. TF whole cell activity was induced
following stimulation with PDGF-BB and PDGF-CC in THP-1 cells. Real-time polymerase chain reaction revealed that ...
Source: Basic Research in Cardiology - September 30, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Is remodeling the dominant compensatory mechanism in both chronic heart failure with preserved and reduced left ventricular ejection fraction?
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This study examines the individual effects of left ventricular hypertrophy, long-axis shortening and the effect of left ventricular
remodeling on ejection fraction, end-diastolic volume and stroke volume using a mathematical model of left ventricular contraction.
Reducing long-axis shortening caused a decline in stroke volume independently of hypertrophy. Increasing concentric left ventricular
hypertrophy resulted in an increase in ejection fraction secondary to augmented wall thickening. A decline in stroke volume
occurred despite a preserved ejection fraction when concentric hypertrophy was present. Normalization of ...
Source: Basic Research in Cardiology - September 24, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Obesity-induced insulin resistance causes endothelial dysfunction without reducing the vascular response to hindlimb ischemia
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Abstract Impairment of vascular growth is a hallmark of diabetic complications but the progression and mechanisms are poorly understood.
To determine whether obesity and early diabetes impair endothelium-dependent vasodilatation and vascular response to ischemia,
microvascular function as well as angiogenic responses to ischemia were assessed in young (C57) and 6-month-old lean mice
(old C57), in obese (db-C57) mice, and in mice suffering an early (db-KsJ) and sustained type 2 diabetes (old db-KsJ). Glycemia gradually increased from the db-C57 to the old db-KsJ. Early and established type II diabetes sig...
Source: Basic Research in Cardiology - September 24, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Aldosterone improves contractile function of adult rat ventricular cardiomyocytes in a non-acute way: potential relationship to the calcium paradox of aldosteronism
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In conclusion, chronic exposure to aldosterone improves
the function of cardiomyocytes under basal conditions and electrolyte disturbances that mimic the situation found in heart
failure patients.
Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-009-0059-6Authors
Sibylle Wenzel, Justus-Liebig-University Giessen Physiologisches Institut Aulweg 129 35392 Giessen GermanyIlhan Tastan, Justus-Liebig-University Giessen Physiologisches Institut Aulweg 129 35392 Giessen GermanyYaser Abdallah, Justus-Liebig-University Giessen Physiologisches Institut Aulweg 129 35392 Giessen GermanyRolf Schreckenb...
Source: Basic Research in Cardiology - September 17, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
AMP579 is revealed to be a potent A2b-adenosine receptor agonist in human 293 cells and rabbit hearts
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Abstract The mixed A1/A2a-adenosine agonist AMP579 given at reperfusion is protective in animal models of myocardial infarction. Receptor-blocking
studies have indicated that the protection came from an adenosine receptor (AR), but neither A1- nor A2a-selective agonists could duplicate its protection. We recently found that A2b-selective agonists given at reperfusion are protective, and, therefore, tested whether AMP579 might also be an A2b agonist. We used human embryonic kidney cells overexpressing human A2b receptors as an assay system. In these cells, A2b receptor occupancy causes phosphorylation of ERK. AM...
Source: Basic Research in Cardiology - September 17, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Humoral anti-proteasomal autoimmunity in dilated cardiomyopathy
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In conclusion, humoral autoreactive anti-proteasome immune responses appear to be enhanced in DCM. Viral infection
of the myocardium may be linked to the induction of anti-proteasomal immunity in DCM.
Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-009-0061-zAuthors
Antje Voigt, Charité-Universitätsmedizin Campus Mitte Medizinische Klinik für Kardiologie und Angiologie Berlin GermanyKatrin Bartel, Charité-Universitätsmedizin Campus Mitte Medizinische Klinik für Kardiologie und Angiologie Berlin GermanyKarl Egerer, Charité-Universitätsmedizin Medizinische Klinik für Rheumatologie ...
Source: Basic Research in Cardiology - September 17, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
K201 improves aspects of the contractile performance of human failing myocardium via reduction in Ca2+ leak from the sarcoplasmic reticulum
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Abstract In heart failure, intracellular Ca2+ leak from cardiac ryanodine receptors (RyR2s) leads to a loss of Ca2+ from the sarcoplasmic reticulum (SR) potentially contributing to decreased function. Experimental data suggest that the 1,4-benzothiazepine
K201 (JTV-519) may stabilise RyR2s and thereby reduce detrimental intracellular Ca2+ leak. Whether K201 exerts beneficial effects in human failing myocardium is unknown. Therefore, we have studied the effects
of K201 on muscle preparations from failing human hearts. K201 (0.3 μM; extracellular [Ca2+]e 1.25 mM) showed no effects on contractile funct...
Source: Basic Research in Cardiology - August 31, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Nitric oxide/cGMP signalling mediates the cardioprotective action of adrenomedullin in reperfused myocardium
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Abstract We demonstrated previously that adrenomedullin (AM), when given during early reperfusion, limited infarct size in rat heart.
The present study was undertaken to provide direct evidence of the NO-dependency of AM’s cardioprotective action by assessing
NO biosynthesis and involvement of the soluble guanylyl cyclase (sGC) pathway. Perfused hearts from male CD-1 mice were subjected
to 30-min left coronary occlusion and 60-min reperfusion. Infarct size was determined by tetrazolium staining. AM 10 nM was
administered from 20 min after coronary occlusion until 10 min after reperfusion. Coronar...
Source: Basic Research in Cardiology - August 28, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Transcriptional regulation of Pim-1 kinase in vascular smooth muscle cells and its role for proliferation
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This study aimed
to foster the understanding of Pim-1 expression and regulation in murine VSMC in response to factors typically present within
the atherosclerotic plaque. While oxidative stress, VEGF-A165 and angiotensin II did not have any effect on Pim-1 expression, VSMC strongly increased (3-fold) Pim-1 mRNA upon stimulation
with PDGFbb, followed by its protein upregulation. Half life of Pim-1 RNA and protein were determined to be 25 min and 6 h, respectively.
PDGFbb induced a strong, 10-fold increase in BrdU-uptake, a marker of proliferation. This was effectively blocked by either Pim-1-specific
inhibito...
Source: Basic Research in Cardiology - August 27, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Long-term treatment with the AT1-receptor antagonist telmisartan inhibits biglycan accumulation in murine atherosclerosis
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Abstract Accumulation of biglycan, a small leucine-rich proteoglycan, in the neointima precedes the retention of lipids and accumulation
of macrophages during early atherosclerosis. Biglycan is therefore considered a pro-atherogenic proteoglycan that might play
a key role in atherogenesis. On the other hand biglycan ensures in part establishment of stable collagen networks. Aim of
the present study was to determine whether telmisartan affects biglycan accumulation in a murine model of accelerated atherosclerosis
and whether collagen matrix is affected. ApoE−/−-mice on Western diet were chronically (12&nb...
Source: Basic Research in Cardiology - August 22, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Transcriptional and posttranscriptional regulators of biglycan in cardiac fibroblasts
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Abstract Biglycan, a small leucine-rich proteoglycan, is essential for scar formation and preservation of hemodynamic function after
myocardial infarction, as shown in biglycan-knockout mice. Because of this important role in cardiac pathophysiology, we aimed
to identify regulators of biglycan expression and posttranslational modifications in cardiac fibroblasts. Cardiac fibroblasts
were isolated from neonatal Wistar-Kyoto rats and used in the first passage. Expression of biglycan was analyzed after metabolic
labeling with [35S]-sulfate by SDS-polyacrylamide gel electrophoresis and molecular sieve chromatogr...
Source: Basic Research in Cardiology - August 22, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Multi-slice computed tomography with N1177 identifies ruptured atherosclerotic plaques in rabbits
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In conclusion, our results show that N1177
is a contrast agent that can identify ruptured atherosclerotic plaques.
Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-009-0052-0Authors
Jozef Leo Van Herck, Antwerp University Hospital Division of Cardiology Wilrijkstraat 10 2650 Edegem BelgiumGuido R. Y. De Meyer, University of Antwerp Division of Pharmacology Universiteitsplein 1 2610 Wilrijk BelgiumWim Martinet, University of Antwerp Division of Pharmacology Universiteitsplein 1 2610 Wilrijk BelgiumRodrigo A. Salgado, Antwerp University Hospital Division of Radiology Wilrijkstraat 10 2650 Ed...
Source: Basic Research in Cardiology - August 19, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Proteasome inhibitor bortezomib promotes a rupture-prone plaque phenotype in ApoE-deficient mice
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In conclusion, our results indicate that an impaired proteasome
function promotes features of a more rupture-prone plaque phenotype.
Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-009-0054-yAuthors
Jozef Leo Van Herck, Antwerp University Hospital Division of Cardiology Wilrijkstraat 10 2650 Edegem BelgiumGuido R. Y. De Meyer, University of Antwerp Division of Pharmacology Universiteitsplein 1 2610 Wilrijk BelgiumWim Martinet, University of Antwerp Division of Pharmacology Universiteitsplein 1 2610 Wilrijk BelgiumHidde Bult, University of Antwerp Division of Pharmacology Universiteitsplei...
Source: Basic Research in Cardiology - August 19, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Attenuation of infarction in cynomolgus monkeys: preconditioning and postconditioning
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Abstract Ischemic pre- (IPC) and post- (IPOC) conditioning are very protective in laboratory animals, but it has not been possible
to measure their anti-infarct potency in human hearts. Non-human primates are genetically closer to humans than other laboratory
animals, but until now there have been no studies of IPC or IPOC in any primate species. Accordingly the left anterior descending
coronary artery of cynomolgus monkeys was occluded for 90 min and reperfused for 4 h. In control animals, only 44% of the
risk zone infarcted indicating cynomolgus myocardium is much more resistant to infarction tha...
Source: Basic Research in Cardiology - August 9, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Protein kinase C α and ε phosphorylation of troponin and myosin binding protein C reduce Ca2+ sensitivity in human myocardium
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This study was designed to reveal and compare the effects
of PKCα- and PKCε-mediated phosphorylation on myofilament function in human myocardium. Isometric force was measured at different
[Ca2+] in single permeabilized cardiomyocytes from failing human left ventricular tissue. Activated PKCα and PKCε equally reduced
Ca2+ sensitivity in failing cardiomyocytes (ΔpCa50 = 0.08 ± 0.01). Both PKC isoforms increased phosphorylation of troponin I- (cTnI) and myosin binding protein C (cMyBP-C)
in failing cardiomyocytes. Subsequent incubation of failing cardiomyocytes with the catalytic subunit of prote...
Source: Basic Research in Cardiology - August 4, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Effects of muscarinic receptor stimulation on Ca2+ transient, cAMP production and pacemaker frequency of rabbit sinoatrial node cells
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In conclusion, muscarinic receptor stimulation inhibits the Cai2+ transient via a cAMP-dependent signaling pathway. Inhibition of the Cai2+ transient contributes to pacemaker slowing and inhibits Cai2+-stimulated cAMP production. Thus, we provide functional evidence for the contribution of the Cai2+ transient to ACh-induced inhibition of pacemaker activity and cAMP content in rabbit SAN cells.
Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-009-0048-9Authors
Marcel M. G. J. van Borren, University of Amsterdam Heart Failure Research Center, Academic Medical Center Amsterdam The NetherlandsA...
Source: Basic Research in Cardiology - July 28, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Propylthiouracil, independent of its antithyroid effect, promotes vascular smooth muscle cells differentiation via PTEN induction
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Abstract Propylthiouracil (PTU), independent of its antithyroid effect, is recently found to have an antiatherosclerotic effect. The
aim of this study is to determine the impact of PTU on phenotypic modulation of vascular smooth muscle cells (VSMCs), as phenotypic
modulation may contribute to the growth of atherosclerotic lesions and neointimal formation after arterial injury. Propylthiouracil
reduced neointimal formation in balloon-injured rat carotid arteries. In vitro, PTU may convert VSMCs from a serum-induced
dedifferentiation state to a differentiated state, as indicated by a spindle-shaped morpho...
Source: Basic Research in Cardiology - July 25, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Sonic hedgehog is a potent chemoattractant for human monocytes: diabetes mellitus inhibits Sonic hedgehog-induced monocyte chemotaxis
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Abstract The aim of the present study was to evaluate the expression of hedgehog (Hh) signaling molecules and the chemotactic activity
of Sonic hedgehog (Shh) in monocytes from control (CTR) and diabetic patients with or without coronary artery disease (CAD).
Previously several studies demonstrated that exogenous administration of Shh can induce angiogenesis and accelerate repair
of ischemic myocardium and skeletal muscles. Blood samples were collected from (1) CTR (n = 25); (2) patients with stable CAD without diabetes mellitus (CAD−DM, n = 10); and (3) with stable CAD with DM (CAD+DM, ...
Source: Basic Research in Cardiology - July 25, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
FGF-inducible 14-kDa protein (Fn14) is regulated via the RhoA/ROCK kinase pathway in cardiomyocytes and mediates nuclear factor-kappaB activation by TWEAK
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Abstract Proinflammatory cytokines, including TNF family members, have been shown to play a critical role in cardiac remodeling. FGF-inducible
14-kDa protein (Fn14, TNFrsf12a or TWEAKR) is the smallest member of the TNF-receptor family. Currently, little is known about
the functional role of Fn14 and its only known ligand TNF-like weak inducer of apoptosis (TWEAK) in the heart. We therefore
evaluated the expression and regulation of Fn14 in cardiomyocytes and in experimental myocardial infarction. In order to study
the regulation of Fn14, myocardial infarction was induced in CD-1 mice and neonatal rat cardio...
Source: Basic Research in Cardiology - July 25, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Attenuation of myocardial injury by postconditioning: role of hypoxia inducible factor-1α
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In conclusion, these data suggest that HIF-1α is involved
in cardioprotection by PostC and pharmacological augmentation of HIF-1α expression that enhances the infarct-sparing effect
of PostC; iNOS, the downstream gene of HIF-1α, may participate in signaling pathways in mediating PostC’s protection.
Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-009-0044-0Authors
Huan-Xin Zhao, Shanxi Medical University Department of Physiology 56 South Xinjian Road 030001 Taiyuan Shanxi People’s Republic of ChinaXiao-Liang Wang, Shanxi Medical University Department of Physiology 56 South Xinjian ...
Source: Basic Research in Cardiology - July 14, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Angiotensin type 1 receptor mediates thyroid hormone-induced cardiomyocyte hypertrophy through the Akt/GSK-3β/mTOR signaling pathway
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Abstract Several studies have implicated the renin angiotensin system in the cardiac hypertrophy induced by thyroid hormone. However,
whether Angiotensin type 1 receptor (AT1R) is critically required to the development of T3-induced cardiomyocyte hypertrophy as well as whether the intracellular mechanisms that are triggered by AT1R are able to contribute to this hypertrophy model is unknown. To address these questions, we employed a selective small interfering
RNA (siRNA, 50 nM) or an AT1R blocker (Losartan, 1 μM) to evaluate the specific role of this receptor in primary cultures of neonatal cardiom...
Source: Basic Research in Cardiology - July 9, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Obesity induced-insulin resistance causes endothelial dysfunction without reducing the vascular response to hindlimb ischemia
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Abstract Impairment of vascular growth is a hallmark of diabetic complications, but the progression and mechanisms are poorly understood.
To determine whether obesity and early diabetes impair endothelium-dependent vasodilatation and vascular response to ischemia,
microvascular function as well as angiogenic responses to ischemia were assessed in young (C57) and 6-month-old lean mice
(old C57), in obese (db-C57) mice, and in mice suffering an early (db-KsJ) and sustained type 2 diabetes (old db-KsJ). Glycemia gradually increased from the db-C57 to the old db-KsJ. Early and established type II diabetes signifi...
Source: Basic Research in Cardiology - June 23, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
The eNOS enhancer AVE 9488: a novel cardioprotectant against ischemia reperfusion injury
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Abstract Nitric oxide (NO) is an important regulator of vascular and myocardial function. Cardiac ischemia/reperfusion injury is reduced
in mice overexpressing endothelial NO synthase (eNOS) suggesting cardioprotection by eNOS. Novel pharmacological substances,
so called eNOS enhancers, upregulate eNOS expression and thereby increase NO production. We tested the effects of the eNOS
enhancer AVE 9488 on cardiac ischemia/reperfusion injury in vivo in mice. After treatment with the eNOS enhancer AVE 9488
(30 mg/kg/day) or placebo for one week mice underwent 30 min of coronary artery ligation and 24&nb...
Source: Basic Research in Cardiology - June 23, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Ischemic postconditioning: experimental models and protocol algorithms
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Abstract Ischemic postconditioning, a simple mechanical maneuver at the onset of reperfusion, reduces infarct size after ischemia/reperfusion.
After its first description in 2003 by Zhao et al. numerous experimental studies have investigated this protective phenomenon.
Whereas the underlying mechanisms and signal transduction are not yet understood in detail, infarct size reduction by ischemic
postconditioning was confirmed in all species tested so far, including man. We have now reviewed the literature with focus
on experimental models and protocols to better understand the determinants of protection by isc...
Source: Basic Research in Cardiology - June 19, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
The cardiac troponin C mutation Leu29Gln found in a patient with hypertrophic cardiomyopathy does not alter contractile parameters in skinned murine myocardium
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In conclusion, no major differences in contractile parameters of preparations
containing hcTnCL29Q compared to hcTnCWT were observed. Therefore, it appears unlikely that hcTnCL29Q induces the development of HCM by affecting the regulation of Ca2+-activated force and interference with PKA-mediated modulation of the Ca2+ sensitivity of contraction.
Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-009-0038-yAuthors
Axel Neulen, University of Cologne Institute of Vegetative Physiology Robert-Koch-Strasse 39 50931 Cologne GermanyRobert Stehle, University of Cologne Institute of Vegetative Physi...
Source: Basic Research in Cardiology - June 9, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Genetic engineering with endothelial nitric oxide synthase improves functional properties of endothelial progenitor cells from patients with coronary artery disease: an in vitro study
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Abstract Recent studies have reported a marked impairment in the number and functions of endothelial progenitor cells (EPCs) in patients
with coronary artery disease (CAD). In view of an important role of eNOS in angiogenesis, in the present study, we evaluated
the effects of eNOS gene transfer in ex vivo expanded EPCs isolated from patients with CAD. The expanded EPCs were transfected
with mammalian expression vector pcDNA3.1-eNOS containing the full-length human eNOS gene using lipofectamine. About 35–40%
of the eNOS–EPCs had higher expression of eNOS as compared to untransfected EPCs. EPCs transfected...
Source: Basic Research in Cardiology - May 29, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Coronary microvascular resistance: methods for its quantification in humans
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Abstract Coronary microvascular dysfunction is a topic that has recently gained considerable interest in the medical community owing
to the growing awareness that microvascular dysfunction occurs in a number of myocardial disease states and has important
prognostic implications. With this growing awareness, comes the desire to accurately assess the functional capacity of the
coronary microcirculation for diagnostic purposes as well as to monitor the effects of therapeutic interventions that are
targeted at reversing the extent of coronary microvascular dysfunction. Measurements of coronary microvascular resi...
Source: Basic Research in Cardiology - May 26, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
The cannabinoid CB1 receptor antagonist, rimonabant, protects against acute myocardial infarction
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Abstract CB1 antagonism is associated with reduced doxorubicin-induced cardiotoxicity and decreased cerebrocortical infarction. Rimonabant,
a selective CB1 receptor antagonist, was, before it was withdrawn, proposed as a treatment for obesity and reported to reduce cardiovascular
risk by improving glucose and lipid profiles and raising adiponectin levels. The cardioprotective actions of rimonabant in
6-week-old C57BL/6J mice fed either high-fat (HFD) or standard diets (STD) for 8 weeks were investigated. At 14 weeks, mice
received rimonabant (10 mg/kg/day, i.p.) or vehicle for 1 week and ...
Source: Basic Research in Cardiology - May 22, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Prevention of vasa vasorum neovascularization attenuates early neointima formation in experimental hypercholesterolemia
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Abstract Vasa vasorum (VV) neovascularization is a key feature of early atherosclerosis and adds substantial endothelial exchange-surface
to the coronary vessel wall. Thus, it is conceivable that VV neovascularization favors the entry of pro-inflammatory and pro-atherosclerotic
blood components into the coronary vessel wall. We sought to investigate the effects of Thalidomide (Th), a potent anti-angiogenic
drug on vasa vasorum (VV) neovascularization, vessel wall inflammation, and neointima formation in early experimental atherosclerosis.
Female domestic swine, 3 months old, were fed normal (N, n =...
Source: Basic Research in Cardiology - May 21, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Cardiac dysfunction in an animal model of neonatal asphyxia is associated with increased degradation of MLC1 by MMP-2
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Abstract The purpose of this study was to determine if decreased heart function after hypoxia followed by reoxygenation (H–R) is associated
with increased degradation of cardiac myosin light chain 1 (MLC1) by matrix metalloproteinase-2 (MMP-2), and to investigate
the effects of the increased level of peroxynitrite in the hearts of H–R animals on MLC1 degradation by MMP-2. Total of 12
newborn piglets were acutely instrumented to monitor cardiac function as assessed by stroke volume. Anesthetized piglets were
block randomized to the normoxic group (n = 6), which received ventilation with room air...
Source: Basic Research in Cardiology - May 19, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Intracoronary acid infusion as an alternative to ischemic postconditioning in pigs
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In conclusion, in pigs submitted to coronary occlusion, intracoronary acid infusion and postconditioning offered
protection against cell death only after prolonged coronary occlusion. Both interventions were equally effective, but intracoronary
acid infusion was associated with high risk of ventricular fibrillation. These results are strongly against translation of
acidic reperfusion to patients with acute myocardial infarction.
Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-009-0032-4Authors
Antonio Rodríguez-Sinovas, Hospital Universitari Vall d’Hebron Laboratorio de Cardiología ...
Source: Basic Research in Cardiology - May 15, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Macrophage depletion suppresses sympathetic hyperinnervation following myocardial infarction
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The objective of the present study was to determine whether macrophages, which are known to synthesize NGF, are necessary
for post-infarct cardiac sympathetic sprouting. Ovariectomized female rats received left coronary artery ligation or sham
operation, followed by intravenous injection of liposomes containing saline vehicle or clodronate, which kills macrophages.
Sham-operated myocardium contained some sympathetic axons, few myofibroblasts and T cells and no CD-68-positive macrophages.
In rats receiving saline liposomes through 7 days post-ligation, the posterolateral infarct border contained numerous myofibrobl...
Source: Basic Research in Cardiology - May 13, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Transcription profiling of HCN-channel isotypes throughout mouse cardiac development
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In conclusion, substantial changes of HCN isotype transcription throughout cardiac
development suggest that a regulated pattern of HCN isotypes is required to establish and ensure a stable heart rhythm. Furthermore,
constantly low HCN transcription in adult myocardium may be required to prevent atrial and ventricular arrhythmogenesis.
Content Type Journal ArticleCategory Original ContributionDOI 10.1007/s00395-009-0031-5Authors
Patrick A. Schweizer, Universitätsklinikum Heidelberg, Innere Medizin III Im Neuenheimer Feld 410 69120 Heidelberg GermanyPessah Yampolsky, Max-Planck-Institut für Medizinische Forschung, A...
Source: Basic Research in Cardiology - May 7, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
The role of transient outward K+ current in electrical remodelling induced by voluntary exercise in female rat hearts
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Abstract Regular exercise can lead to electrical remodelling of the heart. The cellular mechanisms associated with these changes are
not well understood, and are difficult to study in human tissue but are important given that exercise is recommended to the
general population. We have investigated the role played by the transient outward K+ current (I
to) in the changes in electrical activity seen in response to voluntary exercise training in rats. Female rats undertook 6 weeks
of voluntary wheel running exercise (TRN) or were sedentary controls (SED). Monophasic action potentials (MAPs) were recorded
f...
Source: Basic Research in Cardiology - May 5, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Proliferation of neonatal cardiomyocytes by connexin43 knockdown via synergistic inactivation of p38 MAPK and increased expression of FGF1
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In this study, we examined whether and if so how the knockdown of a gap junction protein Cx43 with
siRNA produced changes in the proliferative activity of neonatal cardiomyocytes. Cx43-knockdown resulted in a significant
increase in the proliferation of cardiomyocytes. To clarify the mechanisms behind this increase, we investigated whether the
activity of mitogen-activated protein kinases (MAPKs) changed on knockdown of Cx43. The knockdown decreased the expression
of phosphorylated p38 (p-p38) MAPK. In addition, treatment of cardiomyocytes with a p38 MAPK inhibitor significantly increased the proliferative activity.
C...
Source: Basic Research in Cardiology - April 20, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Ischemic injury and the parathyroid hormone-related protein system: friend or foe?
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Content Type Journal ArticleCategory EDITORIALDOI 10.1007/s00395-009-0784-xAuthors
Klaus-Dieter Schlüter, Justus-Liebig Universität Physiologisches Institut Aulweg 129 35392 Gießen GermanyRolf Schreckenberg, Justus-Liebig Universität Physiologisches Institut Aulweg 129 35392 Gießen Germany
Journal Basic Research in CardiologyOnline ISSN 1435-1803Print ISSN 0300-8428 (Source: Basic Research in Cardiology)
Source: Basic Research in Cardiology - April 20, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Role of extracellular signal-regulated kinase for endothelial progenitor cell dysfunction in coronary artery disease
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Abstract In patients with coronary artery disease (CAD), number and function of endothelial progenitor cells (EPCs) are down-regulated.
The relevant intracellular signalling mechanisms responsible for dysfunction of EPCs in CAD remain poorly characterized. Our
goal was to examine the regulation of ERK-1/2 by SDF-1 and the role of ERK-1/2 for adhesion in EPCs. Western analysis revealed
that the chemokine SDF-1 (SDF-1, 100 nM) mediates phosphorylation of ERK-2 after 90 s with a maximum after 180–300 s in EPCs
isolated from healthy control subjects, while EPCs from patients with CAD are characterize...
Source: Basic Research in Cardiology - April 12, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
STAT-1 decoy oligodeoxynucleotide inhibition of acute rejection in mouse heart transplants
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Abstract During acute rejection of cardiac transplants endothelial cell–leukocyte interaction fuelled by co-stimulatory molecules like
CD40/CD154 may ultimately lead to graft loss. One key player in up-regulating the expression of such pro-inflammatory gene
products is the interferon-γ-dependent transcription factor STAT-1. Hence down-regulating interferon-γ-stimulated pro-inflammatory
gene expression in the graft endothelial cells by employing a decoy oligodeoxynucleotide (dODN) neutralising STAT-1 may protect
the graft. To verify this hypothesis, heterotopic mouse heart transplantation was performed in...
Source: Basic Research in Cardiology - April 8, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Reference change values and determinants of variability of NT-proANP and GDF15 in stable chronic heart failure
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Abstract Biovariability, reference change values (RCV), and index of individuality (IOI) have not been previously described for NT-proANP
or GDF15. Also, the relation of changes of these markers to other clinical variables or biomarkers is unknown. In 41 patients
with stable chronic systolic dysfunction, NT-proANP and GDF15 were measured alongside with clinical variables/markers comprising
NT-proBNP, hsTnT, and hsCRP at four sampling intervals (2 weeks, 1-, 2-, 3-month intervals). At 2 weeks, 1-, 2-, and 3-month-follow-up,
individual NT-proANP variations were 27.1, 22.5, 28.9, 15.6%, respectively, corre...
Source: Basic Research in Cardiology - April 8, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Myocardial inflammation and non-ischaemic heart failure: is there a role for C-reactive protein?
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In this study
we investigated distribution of CRP, the Terminal Complement Complex (C5b-9) and macrophages (CD68) in the myocardium of patients
suffering from non-ischaemic heart failure and their implication on clinical parameters. Endomyocardial biopsies were taken
from 66 patients suffering from dilated cardiomyopathy (DCM). Biopsies were analysed by immunohistochemical and immunofluorescent
staining for CRP, C5b-9 and CD68. Viral DNA/RNA for adenovirus, enterovirus, parvovirus B19 and human herpes virus 6 was detected
by PCR and Southern blot analysis. Myocardial biopsy findings were correlated with plasma level o...
Source: Basic Research in Cardiology - April 3, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
Bone marrow-derived cells are not involved in reendothelialized endothelium as endothelial cells after simple endothelial denudation in mice
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Abstract It has been shown that bone marrow (BM)-derived cells are involved in repaired endothelium induced by a model such as neointima-produced
wire injury in mice. This has not been shown in a less invasive model that results in simple reendothelialization. A new wire-induced
simple endothelial denudation model of the common carotid artery (CCA) of mice, which did not form neointima at 14 days after
the operation, was established. At 7 days after operation, the CCAs were reendothelialized from the aortic arch and the carotid
bifurcation but not completely, shown by whole-mount CD31 immunohistoch...
Source: Basic Research in Cardiology - March 31, 2009 Category: Cardiology Tags: Basic Research in Cardiology Source Type: journals
