Abstract:
AIMS:Hyperhomocysteinaemia is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial dysfunction. Homocysteine modulates cellular methylation reactions. P66shc is a protein that promotes oxidative stress whose expression is governed by promoter methylation. We asked if homocysteine induces endothelial p66shc expression via hypomethylation of CpG dinucleotides in the p66shc promoter, and whether p66shc mediates homocysteine-stimulated endothelial cell dysfunction. METHODS AND RESULTS:Homocysteine stimulates p66shc transcription in human endothelial cells and hypomethylates specific CpG dinucleotides in the human p66shc promoter. Knockdown of p66shc inhibits the increase in reactive oxygen species, and decrease in nitric oxide, elicited by homocysteine in endothelial cells and prevents homocysteine-induced up-regulation of endothelial intercellular adhesion molecule-1. In addition, knockdown of p66shc mitigates homocysteine-induced adhesion of monocytes to endothelial cells. Inhibition of DNA methyltransferase activity or knockdown of DNA methyltransferase 3b abrogates homocysteine-induced up-regulation of p66shc. Comparison of plasma homocysteine in humans with coronary artery disease shows a significant difference between those with highest and lowest p66shc promoter CpG methylation in peripheral blood leucocytes. CONCLUSION:Homocysteine up-regulates human p66shc expression via hypomethylation of specific CpG dinucleotides in the p66shc promoter, and this mechanism is important in homocysteine-induced endothelial cell dysfunction.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Kim CS,Kim YR,Naqvi A,Kumar S,Hoffman TA,Jung SB,Kumar A,Jeon BH,McNamara DM,Irani Kdoi
10.1093/cvr/cvr250subject
Has Abstractpub_date
2011-12-01 00:00:00pages
466-75issue
3eissn
0008-6363issn
1755-3245pii
cvr250journal_volume
92pub_type
杂志文章abstract::The association of nitric oxide (NO) with cardiovascular disease has long been recognized and the extensive research on this topic has revealed both pro- and anti-atherosclerotic effects. While these contradictory findings were initially perplexing recent studies offer molecular mechanisms for the integration of these...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(00)00086-9
更新日期:2000-08-18 00:00:00
abstract:BACKGROUND:In the myocardium, myocyte cell division is irreversibly blocked shortly after birth. The signal that initiates cell cycle withdrawal is unknown. The purpose of this study was to relate changes in expression of beta1 integrin and its associated alpha subunits to cardiomyocyte cell cycle progression during th...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00140-1
更新日期:2000-09-01 00:00:00
abstract:OBJECTIVES:The purpose of this study was to investigate the changes in beta-adrenoceptor density (Bmax) and distribution in a model of chronic myocardial infarction in rats, and to relate possible changes to hemodynamic and neurohumoral abnormalities. In addition, we examined the effects of 8 weeks treatment with ibopa...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract:OBJECTIVE:Experimental evidence suggests that modulation of myocardial substrate metabolism can markedly affect the progression of chronic heart failure (HF). We tested whether the inhibition of carnitine palmitoyl transferase-I (CPT-I), the enzyme regulating mitochondrial fatty acid oxidation, slows left ventricular r...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.02.004
更新日期:2005-06-01 00:00:00
abstract:OBJECTIVE:To determine the effect of Na(+)-H+ exchange blockade on ischemic rigor contracture and reperfusion-induced hypercontracture. METHODS:Thirty-six pigs were submitted to 55 min of coronary occlusion and 5 h reperfusion. Myocardial segment length analysis with ultrasonic microcrystals was used to detect ischemi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00106-5
更新日期:1997-07-01 00:00:00
abstract:OBJECTIVE:The acute administration of growth hormone (GH) or insulin-like growth factor-1 (IGF-1) improves cardiac performance, possibly contributing to the beneficial effects of GH therapy on heart failure (HF). GH can induce the production of IGF-1 and thus the actions of GH may be mediated through its IGF-1 inductio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00058-9
更新日期:1999-07-01 00:00:00
abstract:AIMS:Animal studies show that transforming growth factor-β1 (TGF-β1) is an important mediator of atrial fibrosis and atrial fibrillation (AF). This study investigated the role of TGF-β1 in human AF and the mechanism of atrial-selective fibrosis. METHODS AND RESULTS:Atrial specimens from 17 open heart surgery patients ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt074
更新日期:2013-09-01 00:00:00
abstract::By measuring the coronary sinus blood flow using the thermodilution technique the influence of "thermodilution catheter" withdrawal from the great cardiac vein to the ostium of the coronary sinus was investigated in 41 patients. In addition, the influence of normal and forced respiration on coronary sinus blood flow w...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.1.27
更新日期:1985-01-01 00:00:00
abstract:OBJECTIVES:Matrix metalloproteinases (MMPs) are plausible candidates for prediction of unstable coronary syndromes. We hypothesised that the MMP-3 polymorphism (- 1171, 5A/6A) would relate to coronary plaque characteristics and unstable clinical presentation. METHODS AND RESULTS:Forty patients with de novo presentatio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.05.003
更新日期:2007-09-01 00:00:00
abstract:AIMS:Recent publications have shed new light on the role of the adaptive and innate immune system in the pathogenesis of hypertension. However, there are limited data whether receptors of the innate immune system may influence blood pressure. Toll-like receptor 4 (TLR4), a pattern recognition receptor, is a key compone...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt265
更新日期:2014-03-01 00:00:00
abstract:OBJECTIVES:Diastolic dysfunction that determines symptoms and prognosis in patients with systolic dysfunction causes heart failure even in the absence of systolic dysfunction. Our recent studies have suggested that myocardial stiffening is likely to play a crucial role in triggering deleterious cardiac disorder. This s...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00341-3
更新日期:2002-07-01 00:00:00
abstract::Nitric oxide (NO) is a highly reactive, free radical signalling molecule that is constitutively released in cardiomyocytes by both the endothelial and neuronal isoforms of nitric oxide synthase (eNOS and nNOS, respectively). There are increasing data indicating that NO modulates various proteins involved in excitation...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvm012
更新日期:2008-01-15 00:00:00
abstract:OBJECTIVE:Resveratrol, a natural phytoalexin compound, is present in grapes and wine, and it can produce vasorelaxation. However, little is known of its mechanisms of action on ionic currents in endothelial cells. METHODS:The effect of resveratrol on Ca(2+)-activated K+ currents in an endothelial cell line (HUV-EC-C) ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00397-1
更新日期:2000-03-01 00:00:00
abstract:OBJECTIVE:In heart failure (HF), the generation of reactive oxygen species (ROS) is enhanced. It was shown that failing cardiac myocytes are more susceptible to ROS-induced damage, possibly due to increased expression of the sarcolemmal Na-Ca exchanger (NCX). METHODS:We investigated the consequences of increased expre...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2003.08.006
更新日期:2003-11-01 00:00:00
abstract:AIMS:Atherosclerotic vascular disease has an inflammatory pathogenesis. Heme from intraplaque hemorrhage may drive a protective and pro-resolving macrophage M2-like phenotype, Mhem, via AMPK and ATF1. The anti-diabetic drug metformin may also activate AMPK-dependent signalling. HYPOTHESIS:Metformin systematically indu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa171
更新日期:2020-07-15 00:00:00
abstract:OBJECTIVE:To study the effect of cardiac contraction on left coronary artery pressure-flow relations at different vascular volumes and to compare these relations in the beating heart with those in the heart arrested in systole and diastole. METHODS:Maximally vasodilated, Tyrode perfused, rabbit hearts (n = 6) with an ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00119-9
更新日期:1998-10-01 00:00:00
abstract:AIMS:To compare ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) mortality between Sweden and the UK, adjusting for background population rates of expected death, case mix, and treatments. METHODS AND RESULTS:National data were collected from hospitals in Sweden [n = 73 hospitals, 180 368 pati...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvz197
更新日期:2020-01-01 00:00:00
abstract:AIMS:Our recent work demonstrated that common cardiovascular progenitor cells are characterized and induced by the expression of the transcription factor mesoderm posterior1 (MesP1) in vertebrate embryos and murine embryonic stem cells. As the proliferative potential of stem cell-derived cardiomyocytes is limited, it i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr158
更新日期:2011-10-01 00:00:00
abstract:AIMS:Atherogenesis, evolution of plaque, and outcomes following endovascular intervention depend heavily on the unique vascular architecture of each individual. Patient-specific, multiscale models able to correlate changes in microscopic cellular responses with relevant macroscopic flow, and structural conditions may h...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu124
更新日期:2014-07-01 00:00:00
abstract:OBJECTIVES:The A10 cell line was derived from the thoracic aorta of embryonic rat and is a commonly used model of vascular smooth muscle cells (VSMC). Despite its wide use this cell line has not been well characterized. This is especially important in light of recent evidence of phenotypically distinct cell populations...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00156-9
更新日期:1997-10-01 00:00:00
abstract:OBJECTIVE:Anisotropic conduction characteristics, which may be expressed as the ratio of conduction velocities in the longitudinal (Vlong) and transverse (Vtrans) fibre directions, have been shown to stabilise reentry and favour the induction of sustained, uniform ventricular tachycardia. The aim of this study was to i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)88593-2
更新日期:1995-03-01 00:00:00
abstract::Matricellular proteins are extracellular matrix proteins that modulate cell-matrix interactions and cell function, and do not seem to have a direct structural role. The family includes tenascin-C (TN-C), tenascin-X (TN-X), osteonectin, osteopontin, thrombospondin-1 (TSP1) and thrombospondin-2 (TSP2). Expression of mat...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.06.006
更新日期:2004-10-01 00:00:00
abstract::Diabetic cardiomyopathy is a term used to describe cardiac muscle damage-induced heart failure. Multiple structural and biochemical reasons have been suggested to induce this disorder. The most prominent feature of the diabetic myocardium is attenuated insulin signalling that reduces survival kinases (Akt), potentiall...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvs426
更新日期:2013-03-01 00:00:00
abstract:OBJECTIVE:Resistin belongs to a family of cysteine-rich secreted polypeptides that are mainly produced by monocytes/macrophages in humans. Recently, high concentrations of resistin were shown to induce vascular endothelial dysfunction and vascular smooth muscle cell proliferation. We examined if resistin was secreted f...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.09.015
更新日期:2006-01-01 00:00:00
abstract::Papillary muscles isolated from the left ventricle of 17-20 day old Syrian hamsters with genetic cardiomyopathy (BIO 14.6 strain) were examined for their mechanophysiological response to the beta adrenoceptor agonist isoprenaline. The indices of isometric twitch for both myopathic and aged matched normal (BIO RB strai...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.8.609
更新日期:1986-08-01 00:00:00
abstract::It has long been known that gap junctions are required for the propagation of electrical impulse in the heart. A good deal later, the connexins (Cxs), which are probably exclusive components of the junctional channels that constitute the gap junctions, were identified. More recently, the in vivo functions of cardiac C...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.02.010
更新日期:2004-05-01 00:00:00
abstract:OBJECTIVE:Increased cardiac collagen is seen in uninephrectomised rats made hypertensive by aldosterone infusion and high salt, with the possibility of a direct effect of aldosterone at the level of the cardiac fibroblast. The aim of this study was to examine the effects of aldosterone, glucocorticoids, and angiotensin...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.12.1863
更新日期:1994-12-01 00:00:00
abstract::Isolated, buffer perfused guinea pig hearts were used to study the effects of sotalol on arrhythmias and electrophysiology during 30 min of myocardial ischaemia, induced by reducing coronary flow to 10% of control, and subsequent reperfusion. Action potentials were recorded using the floating microelectrode technique ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/18.7.397
更新日期:1984-07-01 00:00:00
abstract:OBJECTIVES:To elucidate the effect of selective endothelin ET(A)- and mixed ET(A/B)-receptor antagonists on endothelial vasomotor dysfunction in rats with heart failure after myocardial infarction (MI). METHODS:Vasoreactivity and superoxide anion formation were determined in aortic rings from Wistar rats 12 weeks afte...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00083-3
更新日期:2000-07-01 00:00:00
abstract::Eighty-one consecutive patients representing a wide clinical spectrum were studied to assess the degree of limitation of the atrial extrastimulus technique for measurement of atrioventricular node refractoriness; and, to determine the relationship between conductivity and functional refractoriness of the atrioventricu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/16.8.457
更新日期:1982-08-01 00:00:00