Abstract:
BACKGROUND:Despite intensive investigation, how DNA methylation influences endothelial function remains poorly understood. We used methyl-CpG-binding domain protein 2 (MBD2), an interpreter for DNA methylome-encoded information, to dissect the impact of DNA methylation on endothelial function in both physiological and pathophysiological states. METHODS AND RESULTS:Human umbilical vein endothelial cells under normal conditions express moderate levels of MBD2, but knockdown of MBD2 by siRNA significantly enhanced angiogenesis and provided protection against H(2)O(2)-induced apoptosis. Remarkably, Mbd2(-/-) mice were protected against hind-limb ischemia evidenced by the significant improvement in perfusion recovery, along with increased capillary and arteriole formation. Loss of MBD2 activated endothelial survival and proangiogenic signals downstream of vascular endothelial growth factor signaling characterized by an increase in endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor receptor 2 expression, along with enhanced extracellular signal-regulated kinase 1/2 activation and BCL-2 expression. Mechanistic studies confirmed the methylation of CpG elements in the eNOS and vascular endothelial growth factor receptor 2 promoter. MBD2 binds to these methylated CpG elements and suppresses eNOS promoter activity. On ischemic insult, key endothelial genes such as eNOS and vascular endothelial growth factor receptor 2 undergo a DNA methylation turnover, and MBD2 interprets the changes of DNA methylation to suppress their expressions. Moreover, MBD2 modulation of eNOS expression is likely confined to endothelial cells because nonendothelial cells such as splenocytes fail to express eNOS after loss of MBD2. CONCLUSIONS:We provided direct evidence supporting that DNA methylation regulates endothelial function, which forms the molecular basis for understanding how environmental insults (epigenetic factor) affect the genome to modify disease susceptibility. Because MBD2 itself does not affect the methylation of DNA and is dispensable for normal physiology in mice, it could be a viable epigenetic target for modulating endothelial function in disease states.
journal_name
Circulationjournal_title
Circulationauthors
Rao X,Zhong J,Zhang S,Zhang Y,Yu Q,Yang P,Wang MH,Fulton DJ,Shi H,Dong Z,Wang D,Wang CYdoi
10.1161/CIRCULATIONAHA.110.966408subject
Has Abstractpub_date
2011-06-28 00:00:00pages
2964-74issue
25eissn
0009-7322issn
1524-4539pii
CIRCULATIONAHA.110.966408journal_volume
123pub_type
杂志文章相关文献
CIRCULATION文献大全abstract::Patency of the femoral artery of infants and children who previously had percutaneous arterial catheterization at a weight of less than 25 kg was studied angiographically. During the study period, 118 patients had repeat arterial catheterization. 48 from the opposite leg. Femoral artery occlusion was found in four pat...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.56.1.102
更新日期:1977-07-01 00:00:00
abstract::Recent studies have shown that blood flow during closed-chest cardiopulmonary resuscitation (CPR) results primarily from generalized changes in intrathoracic pressure rather than direct compression of the heart. Since ascending aortic and right atrial pressures rise and fall synchronously and to comparable levels duri...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.66.2.297
更新日期:1982-08-01 00:00:00
abstract::To determine whether multiple lead precordial electrocardiographic recordings offer an improved index for noninvasive estimation of left ventricular hemodynamic function and segmental dyssynergy, precordial mapping was performed in patients with anterior myocardial infarction, and the number of pathologic Q waves (gre...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.55.6.833
更新日期:1977-06-01 00:00:00
abstract::To assess the effects on the heart itself of coronary thrombolysis induced with either tissue-type plasminogen activator (t-PA) or streptokinase (SK), we performed positron emission tomography with 11C-palmitate in 19 patients with initial transmural myocardial infarction immediately after admission and again within 4...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.69.5.983
更新日期:1984-05-01 00:00:00
abstract:BACKGROUND:Previous electrophysiological studies in patients with typical atrial flutter suggested that the slow conduction zone might be located in the low right atrial isthmus, which is a path formed by orifice of inferior vena cava, eustachian valve/ridge, coronary sinus ostium, and tricuspid annulus. The conduction...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.96.8.2601
更新日期:1997-10-21 00:00:00
abstract:BACKGROUND:Although the left prepectoral site is preferred for "hot can" placement, this site is unavailable in some patients. We evaluated the influence of electrode location on defibrillation thresholds with alternative hot can and transvenous lead configurations. METHODS AND RESULTS:Three interrelated studies were ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.96.12.4400
更新日期:1997-12-16 00:00:00
abstract:BACKGROUND:Although phase 2 reentry is said to be responsible for initiation of ventricular tachycardia (VT) in Brugada syndrome, information about the activation sequence during VT is limited. METHODS AND RESULTS:We developed an experimental Brugada syndrome model using a canine isolated right ventricular preparation...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000105762.94855.46
更新日期:2004-01-06 00:00:00
abstract:BACKGROUND:Several mechanisms have been advanced to explain Mobitz type II atrioventricular block in the ischemically damaged His-Purkinje system. Only recently, however, has an animal model been developed to study this form of conduction defect in vivo and in vitro. METHODS AND RESULTS:Conduction defects were induced...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.87.4.1389
更新日期:1993-04-01 00:00:00
abstract:BACKGROUND:In this study, we both investigated coronary flow velocity in hypertrophic obstructive cardiomyopathy (HOCM) and tested the hypothesis of differing coronary flow reserve (CFR) of coronary arteries perfusing left ventricular regions with nonuniform myocardial hypertrophy by measuring the relative CFR. METHOD...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.96.3.834
更新日期:1997-08-05 00:00:00
abstract::This review discusses the role of growth factors on the proliferation of smooth muscle cells (SMCs) in injured arteries. We have used a variety of procedures to injure rat carotid arteries and noted that removal of endothelium followed by platelet adherence does not always initiate SMC replication. Furthermore, thromb...
journal_title:Circulation
pub_type: 杂志文章,评审
doi:
更新日期:1992-12-01 00:00:00
abstract:BACKGROUND:We investigated the feasibility and efficacy of polyethylenimine (PEI) based human vascular endothelial growth factor-165 (hVEGF165) gene transfer into human skeletal myoblasts (HSM) for cell based delivery to the infarcted myocardium. METHODS AND RESULTS:Based on optimized transfection procedure using enha...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.106.680124
更新日期:2007-09-11 00:00:00
abstract:BACKGROUND:Regional sympathetic denervation, such as that produced by a myocardial infarction, causes electrophysiological heterogeneity in the ventricles. The purpose of this study was to test the hypothesis that such denervation could cause drugs to exert heterogeneous myocardial effects. METHODS AND RESULTS:Sympath...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.84.4.1709
更新日期:1991-10-01 00:00:00
abstract:BACKGROUND:Failure to differentiate supraventricular from ventricular arrhythmias is the most frequent cause of inappropriate implantable cardioverter-defibrillator therapies. Although a sudden-onset criterion is available to differentiate sustained monomorphic ventricular tachycardias (SMVTs) and sinus tachycardias (S...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.98.7.671
更新日期:1998-08-18 00:00:00
abstract:BACKGROUND:Enteroviruses (EVs) and adenoviruses (ADVs) have been considered common causes of myocarditis and dilated cardiomyopathy. In the present study, we report on the association of parvovirus B19 (PVB19) genomes in the clinical setting of acute myocarditis. METHODS AND RESULTS:This study included 24 consecutive ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000085168.02782.2C
更新日期:2003-08-26 00:00:00
abstract:BACKGROUND:Hypercholesterolemia is associated with endothelial dysfunction. On the basis of the hypothesis that high plasma cholesterol per se may be a sufficient stimulus to upregulate endothelial adhesiveness and that this phenomenon might be reversible, soluble endothelial leukocyte adhesion molecules (sELAMs) were ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.96.5.1381
更新日期:1997-09-02 00:00:00
abstract:BACKGROUND:Recent experimental data indicate that ultrasound-induced destruction of ultrasound contrast microbubbles can cause immediate rupture of the microvessels in which these microbubbles are located. METHODS AND RESULTS:To examine the functional and morphological significance of these findings in the heart, isol...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/hc3001.092038
更新日期:2001-07-24 00:00:00
abstract:BACKGROUND:The angiogenic function of endothelial cells is regulated by numerous mechanisms, but the impact of long noncoding RNAs (lncRNAs) has hardly been studied. We set out to identify novel and functionally important endothelial lncRNAs. METHODS:Epigenetically controlled lncRNAs in human umbilical vein endothelia...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.116.026991
更新日期:2017-07-04 00:00:00
abstract:BACKGROUND:The objective of this study was to determine the impact of concurrent cardiac procedures (CCP) on patient outcomes after HeartMate II (HMII) left ventricular assist device implantation. METHODS AND RESULTS:Two hundred eighty-one patients underwent implantation of a HMII as a bridge to transplantation from M...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.108.844274
更新日期:2009-09-15 00:00:00
abstract::Two guidelines from the American College of Cardiology (ACC), the American Heart Association (AHA), and collaborating societies address the risk of aortic dissection in patients with bicuspid aortic valves and severe aortic enlargement: the "2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIR.0000000000000331
更新日期:2016-02-16 00:00:00
abstract:BACKGROUND:Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) has been used to measure T2* changes in skeletal muscle tissue of healthy volunteers. The BOLD effect is assumed to primarily reflect changes in blood oxygenation at the tissue level. We compared the calf muscle BOLD response of patien...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.105.605717
更新日期:2006-06-27 00:00:00
abstract:BACKGROUND:This experiment sought to determine the effects of fish oil on superoxide anion production in the myocardium and coronary arteries of atherosclerotic monkeys. Recent evidence indicates that dietary supplementation with fish oil preserves normal vasomotion of atherosclerotic coronary arteries and reduces dama...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.91.4.1123
更新日期:1995-02-15 00:00:00
abstract:BACKGROUND:The estrogen receptor-alpha (ER-alpha) IVS1-401 polymorphism identifies a group of women (approximately 20%) who have augmented effects of hormone replacement therapy (HRT) on levels of HDL cholesterol. This study sought to determine if this augmentation extends to HRT regulation of E-selectin and C-reactive...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.0000016173.98826.88
更新日期:2002-04-23 00:00:00
abstract:BACKGROUND:An inverse association between height and risk of coronary heart disease (CHD) has been reported in several case-control and cohort studies, but the reasons for the association remain uncertain. We evaluated this association among 22,071 male physicians, a population homogeneous for high educational attainme...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.88.4.1437
更新日期:1993-10-01 00:00:00
abstract:BACKGROUND:Patients with transfusional iron overload may develop a life-limiting cardiomyopathy. The sensitivity of lipid-metabolizing enzymes to peroxidative injury, as well as the reported effects of arachidonic acid (AA) and metabolites on cardiac rhythm, led us to hypothesize that iron-overloaded cardiomyocytes dis...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.103.19.2395
更新日期:2001-05-15 00:00:00
abstract:BACKGROUND:Pulmonary hypertension (PH) is a life-threatening disease. Bone marrow cell transplantation is reported to reduce the development of PH by increasing vascular beds in pulmonary circulation. However, adenoviral overexpression of endothelial nitric oxide synthase (eNOS) in the lung is also known to reduce PH. ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.105.001487
更新日期:2006-07-04 00:00:00
abstract:BACKGROUND:We hypothesized that cytomegalovirus (CMV) may contribute to the vasculopathy observed in cardiac allograft recipients by impairing the endothelial nitric oxide synthase pathway. We focused on asymmetric dimethylarginine (ADMA, the endogenous inhibitor of nitric oxide synthase) as a potential mediator of the...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000109692.16004.AF
更新日期:2004-02-03 00:00:00
abstract::A reduced rate of diastolic closure of the anterior mitral leaflet has been shown to occur in mitral stenosis, primary pulmonary hypertension, and in cases with reduced left ventricular compliance. Posterior notion of the posterior mitral leaflet in diastole has been the distinguishing feature to rule out the diagnosi...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.51.3.511
更新日期:1975-03-01 00:00:00
abstract:BACKGROUND:Retrospective studies in dialysis patients have reported increased survival after coronary artery bypass (CAB) compared with coronary artery stenting and PTCA. The purpose of this study was to compare the long-term outcome of renal transplant recipients after stent, PTCA, or CAB with or without internal mamm...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000129317.12580.68
更新日期:2004-06-15 00:00:00
abstract::Background-Homozygosity for a relatively common Cys282Tyr mutation of the human hemochromatosis-associated (HFE) gene was recently found to account for most cases of hereditary hemochromatosis. Because excess iron has been postulated to enhance risk of vascular disease, we studied whether occurrence of this mutation w...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.100.12.1274
更新日期:1999-09-21 00:00:00
abstract:BACKGROUND:The cross-talk between vascular endothelial growth factor (VEGF)-A, angiopoietin (Ang), and VE-cadherin coregulates endothelial cell (EC) survival. Cardiac expression of VEGF-A but not its receptor KDR is blunted in dilated cardiomyopathy (DCM). Whether VE-cadherin/Ang function is affected in DCM is unknown....
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000091085.12422.19
更新日期:2003-09-30 00:00:00