Abstract:
RATIONALE:Atherosclerosis proceeds through a multistep reaction that begins with endothelial injury caused by a host of stress signals, among which oxidized low-density lipoprotein (oxLDL) plays a critical role. OxLDL disrupts normal functionality of the endothelium by upregulating adhesion molecules (eg, ICAM-1) and concomitantly downregulating endothelial nitric oxide synthase (eNOS) expression. The transcriptional modulator that mediates the cellular response to oxLDL remains largely obscure. OBJECTIVE:Our goal was to determine whether myocardin-related transcription factor (MRTF)-A, a key protein involved in the transcriptional regulation of smooth muscle cell phenotype, is responsible for the endothelial injury by oxLDL, and, if so, how MRTF-A promotes the proatherogenic agenda initiated by oxLDL. METHODS AND RESULTS:OxLDL stimulated the expression of MRTF-A in endothelial cells as evidenced by Western blotting and immunofluorescence. Overexpression of MRTF-A synergistically enhanced the induction of ICAM-1 and suppression of eNOS by oxLDL. In contrast, disruption of MRTF-A, either by small interfering RNA or dominant negative mutation, abrogated the pathogenic program triggered by oxLDL. Finally, chromatin immunoprecipitation assays indicate that oxLDL preferentially augmented MRTF-A binding to ICAM-1 and eNOS promoters and that MRTF-A drove differential epigenetic alterations taking place on these promoters in response to oxLDL. CONCLUSIONS:Therefore, our data provide the first demonstration that MRTF-A is critically linked to pivotal pathophysiological events in the vascular endothelium.
journal_name
Circ Resjournal_title
Circulation researchauthors
Fang F,Yang Y,Yuan Z,Gao Y,Zhou J,Chen Q,Xu Ydoi
10.1161/CIRCRESAHA.111.240655subject
Has Abstractpub_date
2011-04-01 00:00:00pages
797-807issue
7eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.111.240655journal_volume
108pub_type
杂志文章abstract::We studied the role of copper as a potential mediator of postischemic reperfusion injury in the isolated, perfused rat heart. Hearts were equilibrated with Krebs-Henseleit buffer for 10 minutes and then loaded with copper by way of perfusion with buffer containing 20 microM copper(II)-bis-histidial for 30 minutes. Con...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.3.881
更新日期:1991-09-01 00:00:00
abstract::Although estradiol (E(2)) has been recognized to exert several vasculoprotective effects in several species, its effects in mouse vasomotion are unknown, and consequently, so is the estrogen receptor subtype mediating these effects. We investigated the effect of E(2) (80 microg/kg/day for 15 days) on NO production in ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh0402.105096
更新日期:2002-03-08 00:00:00
abstract::Mitochondria have long been known to play a critical role in maintaining the bioenergetic status of cells under physiological conditions. It was also recognized early in mitochondrial research that the reduction of oxygen to generate the free radical superoxide occurs at various sites in the respiratory chain and was ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000248212.86638.e9
更新日期:2006-10-27 00:00:00
abstract::The hypothesis that neurally mediated coronary vasodilation occurs as part of the carotid baroreceptor reflex was investigated. The left main coronary artery was cannulated and perfused at constant pressure (100 mm Hg) in closed-chest, chloralose-anesthetized dogs. The heart was paced at a constant rate between 60 and...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.4.486
更新日期:1985-04-01 00:00:00
abstract:RATIONALE:A better understanding of the mechanism underlying skeletal muscle repair is required to develop therapies that promote tissue regeneration in adults. Hedgehog signaling has been shown previously to be involved in myogenesis and angiogenesis: 2 crucial processes for muscle development and regeneration. OBJEC...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.113.301546
更新日期:2013-10-25 00:00:00
abstract:RATIONALE:Mutations in GJC2 and GJA1, encoding Cxs (connexins) 47 and 43, respectively, are linked to lymphedema, but the underlying mechanisms are unknown. Because efficient lymph transport relies on the coordinated contractions of lymphatic muscle cells (LMCs) and their electrical coupling through Cxs, Cx-related lym...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.312576
更新日期:2018-09-28 00:00:00
abstract::Oxidized phospholipids, including oxidation products of palmitoyl-arachidonyl-phosphatidyl choline (PAPC), are mediators of inflammation in endothelial cells (ECs) and known to induce several chemokines, including interleukin-8 (IL-8). In this study, we show that oxidized PAPC (OxPAPC), which accumulates in atheroscle...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000146030.53089.18
更新日期:2004-10-15 00:00:00
abstract::Muscle ring finger (MuRF) proteins have been implicated in transmitting mechanical forces to cell signaling pathways through their interactions with the giant protein titin. Recent evidence has linked mechanically-induced stimuli with the control of serum response factor activity and localization through MuRF2. This o...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000259559.48597.32
更新日期:2007-03-02 00:00:00
abstract::We used a genetic approach to determine whether increasing the level of A3 adenosine receptors (A3ARs) expressed in the heart confers protection against ischemia without causing cardiac pathology. We generated mice carrying one (A3tg.1) or six (A3tg.6) copies of a transgene consisting of the cardiomyocyte-specific alp...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000028007.91385.ee
更新日期:2002-07-26 00:00:00
abstract::The circulatory effects associated with lifelong plasma atrial natriuretic factor (ANF) elevation were examined by generating transgenic mice, which constitutively express a fusion gene consisting of the transthyretin promoter and the ANF structural gene. These mice have chronically elevated ANF levels as compared wit...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.4.747
更新日期:1994-04-01 00:00:00
abstract::Optimistic people have reduced risk for cardiovascular disease and cardiovascular-related mortality compared with their less optimistic peers. One explanation for this is that optimistic people may be more likely to engage in healthy behavior like exercising frequently, eating fruits and vegetables, and avoiding cigar...
journal_title:Circulation research
pub_type: 杂志文章,meta分析,评审
doi:10.1161/CIRCRESAHA.117.310828
更新日期:2018-04-13 00:00:00
abstract:RATIONALE:Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of acquired heart disease in childhood; however, diagnosing KD can be difficult. OBJECTIVE:To identify unique proteomic biomarkers that can be used to facilitate earlier diagnosis of KD. METHODS AND RESULTS:We enrolled 214 children...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.305834
更新日期:2015-02-27 00:00:00
abstract:RATIONALE:Patients with chronic kidney disease (CKD) develop hyperhomocysteinemia and have a higher cardiovascular mortality than those without hyperhomocysteinemia by 10-fold. OBJECTIVE:We investigated monocyte differentiation in human CKD and cardiovascular disease (CVD). METHODS AND RESULTS:We identified CD40 as a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.308750
更新日期:2016-11-11 00:00:00
abstract::Recent evidence suggests that functional diversity of vascular smooth muscle is produced in part by a differential expression of ion channels. The aim of the present study was to examine the role of Ca(2+)-activated K(+) channels (K(Ca) channels) in the expression of smooth muscle cell functional phenotype. We found t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.9.e33
更新日期:1999-10-29 00:00:00
abstract::Adipose tissue (AT) plays a central role in both metabolic health and pathophysiology. Its expansion in obesity results in increased mortality and morbidity, with contributions to cardiovascular disease, diabetes mellitus, fatty liver disease, and cancer. Obesity prevalence is at an all-time high and is projected to b...
journal_title:Circulation research
pub_type: 评审
doi:10.1161/CIRCRESAHA.120.316203
更新日期:2020-05-22 00:00:00
abstract::Inherited restrictive cardiomyopathy (RCM) is a debilitating disease characterized by a stiff heart with impaired ventricular relaxation. Mutations in cardiac troponin I (cTnI) were identified as causal for RCM. Acute genetic engineering of adult cardiac myocytes was used to identify primary structure/function effects...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000268412.34364.50
更新日期:2007-05-25 00:00:00
abstract::Transforming growth factor (TGF)-beta(1) is a potent stimulator of intimal growth. We showed previously that TGF-beta(1) stimulates intimal growth through early upregulation of plasminogen activator inhibitor-1 (PAI-1) and, subsequently, PAI-1-dependent increases in cell migration and matrix accumulation. We also show...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000266970.34017.8d
更新日期:2007-05-11 00:00:00
abstract::The accumulation of inositol 1,4,5-trisphosphate (IP3) after hormonal stimulation has a physiological role, possibly by alteration of Ca2+ levels in cardiac myocyte. However, this accumulation has not been studied under pathophysiological conditions. In this report, we examine phosphatidylinositol metabolism during ce...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.5.966
更新日期:1993-05-01 00:00:00
abstract::Three models of altered autonomic innervation of the chick heart have been developed in the last few years. These include sympathetically aneural heart, parasympathetically aneural heart, and heart with cholinergic innervation reconstituted from the nodose placodes. The neural status of these hearts has been assessed ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.6.1547
更新日期:1989-12-01 00:00:00
abstract:RATIONALE:Human heregulins, neuregulin-1 type I polypeptides that activate proliferation, differentiation, and survival of glial cells, neurons, and myocytes, are expressed in macrophage foam cells within human coronary atherosclerotic lesions. Macrophage foam cell formation, characterized by cholesterol ester accumula...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.193870
更新日期:2009-08-28 00:00:00
abstract::MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate about 30% of the encoding genes of the human genome. However, the role of miRNAs in vascular disease is currently completely unknown. Using microarray analysis, we demonstrated for the first time that miRNAs are aberr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.106.141986
更新日期:2007-06-08 00:00:00
abstract::The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves substantial proteolysis of the arterial extracellular matrix. The lysosomal cysteine proteases can exert potent elastolytic and collagenolytic activity. Human atherosclerotic plaques have increased cysteine protease content and decreased levels...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000155964.34150.F7
更新日期:2005-02-18 00:00:00
abstract::Increased activity of matrix metalloproteinases (MMPs) has been implicated in numerous disease processes, including tumor growth and metastasis, arthritis, and periodontal disease. It is now becoming increasingly clear that extracellular matrix degradation by MMPs is also involved in the pathogenesis of cardiovascular...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/hh1501.094396
更新日期:2001-08-03 00:00:00
abstract::Vascular endothelial growth factors (VEGFs) and their receptors have emerged as central regulators of the angiogenic process. However, involvement of VEGF-B, one of these factors, in angiogenesis remains obscure. Mice received subcutaneous injection of Matrigel alone or Matrigel with human recombinant protein rhVEGF-B...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000081594.21764.44
更新日期:2003-07-25 00:00:00
abstract::Cell-cell communication has proven to be even more complex than previously thought since the discovery that extracellular vesicles serve as containers of biological information on various pathophysiological settings. Extracellular vesicles are classified into exosomes, microvesicles/microparticles, or apoptotic bodies...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300858
更新日期:2014-01-17 00:00:00
abstract::We have investigated the actions of vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) on the pacemaker current (I(f)) in canine Purkinje fibers. On voltage pulses to the middle of the I(f) activation range, VIP reversibly increases I(f), whereas NPY reversibly decreases I(f). A three-pulse voltage protocol ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.1.157
更新日期:1994-01-01 00:00:00
abstract::The fat-derived hormone adiponectin has been shown to have a protective role in macrovascular disorders. However, nothing is known about the function of adiponectin in retinal microvessel disease. Here, we investigated the causal role of adiponectin in retinal vessel formation and inflammation under conditions of hypo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.194506
更新日期:2009-05-08 00:00:00
abstract::We have measured the apparent Ca2+ sensitivities of force development in skinned cardiac trabeculae at different sarcome lengths together with shifts in troponin (Tn) T subunits on specimens from the same hearts and drawn insights into the pathogenesis of myocardial dysfunction in the diabetic rat. The Ca(2+)-force re...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.4.600
更新日期:1995-04-01 00:00:00
abstract::Smaller Ca2+ transients and systolic dysfunction in heart failure (HF) can be largely explained by reduced total sarcoplasmic reticulum (SR) Ca2+ content ([Ca]SRT). However, it is unknown whether low [Ca]SRT is manifest as reduced: (1) intra-SR free [Ca2+] ([Ca2+]SR), (2) intra-SR Ca2+ buffering, or (3) SR volume (as ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.152140
更新日期:2007-10-12 00:00:00
abstract:RATIONALE:Macrophages are essential regulators of atherosclerosis. They secrete cytokines, process lipoproteins and cholesterol, and take up apoptotic cells. Multiple subsets of plaque macrophages exist and their differential roles are emerging. OBJECTIVE:Here, we explore macrophage heterogeneity in atherosclerosis pl...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.315175
更新日期:2019-12-06 00:00:00