Myocardin-related transcription factor A mediates OxLDL-induced endothelial injury.


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.


Circ Res


Circulation research


Fang F,Yang Y,Yuan Z,Gao Y,Zhou J,Chen Q,Xu Y




Has Abstract


2011-04-01 00:00:00














  • Intrarenal renin-angiotensin-sodium interdependent mechanism controlling postclamp renal artery pressure and renin release in the conscious dog with chronic one-kidney Goldblatt hypertension.

    abstract::We studied postclamp renal artery pressure and renin release in eight conscious dogs with one-kidney Goldblatt hypertension. On normal sodium intake, intrarenal blockade of angiotensin II with Sar1-Ala8-angiotension II (P-113, saralasin acetate) markedly decreased postclamp renal artery pressure and increased renin re...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Ayers CR,Katholi RE,Vaughan ED Jr,Carey RM,Kimbrough HM Jr,Yancey MR,Morton CL

    更新日期:1977-03-01 00:00:00

  • Renal myogenic response: kinetic attributes and physiological role.

    abstract::The kinetic attributes of the afferent arteriole myogenic response were investigated using the in vitro perfused hydronephrotic rat kidney. Equations describing the time course for pressure-dependent vasoconstriction and vasodilation, and steady-state changes in diameter were combined to develop a mathematical model o...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Loutzenhiser R,Bidani A,Chilton L

    更新日期:2002-06-28 00:00:00

  • The identification of nitric oxide as endothelium-derived relaxing factor.

    abstract::The identification of endothelium-derived relaxing factor as nitric oxide (NO) dramatically altered the course of vascular biology, as well as other biomedical disciplines. The ubiquity of this natural product of cell metabolism and the complexity of its biochemistry provide a rich source of molecular mediators of phe...

    journal_title:Circulation research

    pub_type: 杂志文章,评审


    authors: Loscalzo J

    更新日期:2013-07-05 00:00:00

  • Arterial Stiffness Preceding Diabetes: A Longitudinal Study.

    abstract:RATIONALE:Previous studies on the relationship between diabetes and arterial stiffness were mostly cross-sectional. A few longitudinal studies focused on one single direction. Whether the association between arterial stiffness and diabetes is bidirectional remains unclear to date. OBJECTIVE:To explore the temporal rel...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Zheng M,Zhang X,Chen S,Song Y,Zhao Q,Gao X,Wu S

    更新日期:2020-12-04 00:00:00

  • Phosphorylation of endothelial nitric oxide synthase in response to fluid shear stress.

    abstract::Endothelial cells release nitric oxide (NO) more potently in response to increased shear stress than to agonists which elevate intracellular free calcium concentration ([Ca2+]i). To determine mechanistic differences in the regulation of endothelial constitutive NO synthase (ecNOS), we measured NO production by bovine ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Corson MA,James NL,Latta SE,Nerem RM,Berk BC,Harrison DG

    更新日期:1996-11-01 00:00:00

  • Thin filament mutations: developing an integrative approach to a complex disorder.

    abstract::Sixteen years ago, mutations in cardiac troponin (Tn)T and α-tropomyosin were linked to familial hypertrophic cardiomyopathy, thus transforming the disorder from a disease of the β-myosin heavy chain to a disease of the cardiac sarcomere. From the outset, studies suggested that mutations in the regulatory thin filamen...

    journal_title:Circulation research

    pub_type: 杂志文章,评审


    authors: Tardiff JC

    更新日期:2011-03-18 00:00:00

  • Pitx2c and Nkx2-5 are required for the formation and identity of the pulmonary myocardium.

    abstract::The pulmonary vein is sleeved by myocardium, which is a major source of atrial fibrillation and is involved in congenital sinus venosus defects. Little is known about the cellular origin and mechanism of formation of the pulmonary myocardium. We observed a biphasic process of pulmonary myocardium formation in mice. Fi...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Mommersteeg MT,Brown NA,Prall OW,de Gier-de Vries C,Harvey RP,Moorman AF,Christoffels VM

    更新日期:2007-10-26 00:00:00

  • Inhibition of sarcolemmal carbon-centered free radical formation by propranolol.

    abstract::The mechanism of propranolol-inhibited sarcolemmal membrane lipid peroxidation was investigated by electron spin resonance spin-trapping technique using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 2-methyl-2-nitrosopropane (MNP). Highly purified canine myocytic sarcolemma were peroxidized by a superoxide-driven (from ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Mak IT,Arroyo CM,Weglicki WB

    更新日期:1989-10-01 00:00:00

  • Preparation, characterization, and evaluation of a monoclonal antibody against the rabbit platelet glycoprotein IIb/IIIa in an experimental angioplasty model.

    abstract::The deposition of platelets at the site of balloon angioplasty is thought to play a major role in the pathogenesis of restenosis. The antibody AZ-1, which binds to the rabbit platelet glycoprotein IIb/IIIa receptor and inhibits platelet function both in vitro and in vivo, was produced and tested in an experimental mod...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Azrin MA,Ling FS,Chen Q,Pawashe A,Migliaccio F,Homer R,Todd M,Ezekowitz MD

    更新日期:1994-08-01 00:00:00

  • Vascular remodeling and improvement of coronary reserve after hydralazine treatment in spontaneously hypertensive rats.

    abstract::The purpose of these studies was to evaluate cardiovascular structural and functional changes in a model of hypertension-induced myocardial hypertrophy in which vasodilator therapy decreased blood pressure to normal levels. Thus, we determined the separate contributions of hypertension and hypertrophy on myocardial an...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Anderson PG,Bishop SP,Digerness SB

    更新日期:1989-06-01 00:00:00

  • Familial hypertrophic cardiomyopathy-linked mutant troponin T causes stress-induced ventricular tachycardia and Ca2+-dependent action potential remodeling.

    abstract::The cardiac troponin T (TnT) I79N mutation has been linked to familial hypertrophic cardiomyopathy and high incidence of sudden death, despite causing little or no cardiac hypertrophy in patients. Transgenic mice expressing mutant human TnT (I79N-Tg) have increased cardiac contractility, but no ventricular hypertrophy...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Knollmann BC,Kirchhof P,Sirenko SG,Degen H,Greene AE,Schober T,Mackow JC,Fabritz L,Potter JD,Morad M

    更新日期:2003-03-07 00:00:00

  • Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial.

    abstract:RATIONALE:Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, selected patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear. OBJECTIVE:The purpose of ...

    journal_title:Circulation research

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Schutt RC,Trachtenberg BH,Cooke JP,Traverse JH,Henry TD,Pepine CJ,Willerson JT,Perin EC,Ellis SG,Zhao DX,Bhatnagar A,Johnstone BH,Lai D,Resende M,Ebert RF,Wu JC,Sayre SL,Orozco A,Zierold C,Simari RD,Moyé L,Cogle

    更新日期:2015-01-02 00:00:00

  • Molecular mechanisms of mitochondrial autophagy/mitophagy in the heart.

    abstract::Mitochondrial quality is a crucial determinant of cell viability, and mitochondrial autophagy plays a central role in this control mechanism. Based on studies in yeast, numerous investigations of this process have been conducted, and the framework of mammalian mitochondrial autophagy is progressively appearing. Howeve...

    journal_title:Circulation research

    pub_type: 杂志文章,评审


    authors: Saito T,Sadoshima J

    更新日期:2015-04-10 00:00:00

  • Substructure of intercellular junctions in freeze-fractured alveolar-capillary membranes of mouse lung.

    abstract::The purpose of this study was to examine by freeze-fracture the ultrastructure of intercellular junctions between mouse pulmonary endothelial and epithelial cells, and to relate this fine structure to that deduced from previous physiological and ultrastructural studies using tracer techniques. Junctions between capill...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Schneeberger EE,Karnovsky MJ

    更新日期:1976-05-01 00:00:00

  • Renal afferents signaling diuretic activity in the cat.

    abstract::Mechanoreceptors and chemoreceptors have been identified inside the kidney, but their functional role is still largely unclear. The aim of this study was to investigate whether changes in urine output could modify the discharge rate of renal afferent fibers. Experiments were performed in anesthetized cats in which aff...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Genovesi S,Pieruzzi F,Wijnmaalen P,Centonza L,Golin R,Zanchetti A,Stella A

    更新日期:1993-11-01 00:00:00

  • The Calcineurin-TFEB-p62 Pathway Mediates the Activation of Cardiac Macroautophagy by Proteasomal Malfunction.

    abstract:RATIONALE:The ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway are pivotal to proteostasis. Targeting these pathways is emerging as an attractive strategy for treating cancer. However, a significant proportion of patients who receive a proteasome inhibitor-containing regime show cardiotoxicity. Mo...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Pan B,Li J,Parajuli N,Tian Z,Wu P,Lewno MT,Zou J,Wang W,Bedford L,Mayer RJ,Fang J,Liu J,Cui T,Su H,Wang X

    更新日期:2020-07-31 00:00:00

  • The intersection between aging and cardiovascular disease.

    abstract::The average lifespan of humans is increasing, and with it the percentage of people entering the 65 and older age group is growing rapidly and will continue to do so in the next 20 years. Within this age group, cardiovascular disease will remain the leading cause of death, and the cost associated with treatment will co...

    journal_title:Circulation research

    pub_type: 杂志文章,评审


    authors: North BJ,Sinclair DA

    更新日期:2012-04-13 00:00:00

  • Cardiac sympathetic afferent cell bodies are located in the peripheral nervous system of the cat.

    abstract::Studies of the stellate ganglion and middle cervical ganglion indicate that sympathetic efferent nerve activity can be modified by peripheral excitatory inputs and that these neural connections may function as pathways for a peripheral reflex at the level of the thoracic sympathetic ganglia. This excitatory synaptic i...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Bosnjak ZJ,Kampine JP

    更新日期:1989-03-01 00:00:00

  • Thin filament disinhibition by restrictive cardiomyopathy mutant R193H troponin I induces Ca2+-independent mechanical tone and acute myocyte remodeling.

    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


    authors: Davis J,Wen H,Edwards T,Metzger JM

    更新日期:2007-05-25 00:00:00

  • Hydrogen peroxide decreases pHi in human aortic endothelial cells by inhibiting Na+/H+ exchange.

    abstract::Postischemic endothelial dysfunction may occur as a result of the effects of endogenous oxidants like hydrogen peroxide. Since endothelium-dependent vasodilator function may be affected by pHi, the effect of hydrogen peroxide on endothelial pHi was examined. Hydrogen peroxide (100 micromol/L for 10 minutes) decreased ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Hu Q,Xia Y,Corda S,Zweier JL,Ziegelstein RC

    更新日期:1998-09-21 00:00:00

  • Role of CaVbeta subunits, and lack of functional reserve, in protein kinase A modulation of cardiac CaV1.2 channels.

    abstract::Protein kinase A (PKA)-mediated enhancement of L-type calcium currents (I(Ca,L)) is essential for sympathetic regulation of the heartbeat and is the classic example of channel regulation by phosphorylation, and its loss is a common hallmark of heart failure. Mechanistic understanding of how distinct Ca(V) channel subu...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Miriyala J,Nguyen T,Yue DT,Colecraft HM

    更新日期:2008-04-11 00:00:00

  • Role of sodium and calcium dysregulation in tachyarrhythmias in sudden cardiac death.

    abstract::Despite improvements in the therapy of underlying heart disease, sudden cardiac death is a major cause of death worldwide. Disturbed Na and Ca handling is known to be a major predisposing factor for life-threatening tachyarrhythmias. In cardiomyocytes, many ion channels and transporters, including voltage-gated Na and...

    journal_title:Circulation research

    pub_type: 杂志文章,评审


    authors: Wagner S,Maier LS,Bers DM

    更新日期:2015-06-05 00:00:00

  • Intra-sarcoplasmic reticulum free [Ca2+] and buffering in arrhythmogenic failing rabbit heart.

    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


    authors: Guo T,Ai X,Shannon TR,Pogwizd SM,Bers DM

    更新日期:2007-10-12 00:00:00

  • Stimulation of fibroblast collagen and total protein formation by an endothelial cell-derived factor.

    abstract::We investigated the effect of medium conditioned by bovine aortic endothelial cells on collagen accumulation and total protein formation by human embryonic fibroblasts or bovine smooth muscle cells in cultures. The conditioned medium at a 1:10 dilution induced a twofold increase in collagen and total protein accumulat...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Villanueva AG,Farber HW,Rounds S,Goldstein RH

    更新日期:1991-07-01 00:00:00

  • Nitric oxide donors induce late preconditioning against myocardial stunning and infarction in conscious rabbits via an antioxidant-sensitive mechanism.

    abstract::The goal of this study was to test the hypothesis that the cardioprotective effects of the late phase of ischemic preconditioning (PC) can be mimicked by treatment with NO donors. In phase I (studies of myocardial stunning), conscious rabbits underwent a sequence of six 4-minute coronary occlusion/4-minute reperfusion...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Takano H,Tang XL,Qiu Y,Guo Y,French BA,Bolli R

    更新日期:1998-07-13 00:00:00

  • The distribution of blood rheological parameters in the microvasculature of cat mesentery.

    abstract::In vivo studies of the rheological behavior of blood in the microcirculation were conducted by direct in situ measurements in cat mesentery. Upstream to downstream pressure drops were measured in unbranched arterioles, capillaries, and venules, with diameters from 7 to 58 micrometer. Simultaneous measurements of red c...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Lipowsky HH,Kovalcheck S,Zweifach BW

    更新日期:1978-11-01 00:00:00

  • Enhancement of potassium-sensitive current in heart cells by pinacidil. Evidence for modulation of the ATP-sensitive potassium channel.

    abstract::Pinacidil belongs to a novel group of compounds that enhance the potassium permeability of vascular smooth muscle. Evidence also exists that this drug enhances the potassium permeability of cardiac tissue. The purpose of the present investigation was to determine if pinacidil alters potassium-channel activity in heart...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Arena JP,Kass RS

    更新日期:1989-08-01 00:00:00

  • Strongly binding myosin crossbridges regulate loaded shortening and power output in cardiac myocytes.

    abstract::This study investigated the possible roles of strongly binding myosin crossbridges in determining loaded shortening and power output in cardiac myocytes. Single skinned cardiac myocytes were attached between a force transducer and position motor, and shortening velocities were measured over a range of loads during var...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: McDonald KS,Moss RL

    更新日期:2000-10-27 00:00:00

  • Differences in the determinants of overdrive suppression between sinus rhythm and slow atrioventricular junctional rhythm.

    abstract::Sinus node recovery time was compared to the recovery time of a slow atrioventricular junctional rhythm in each of the same seven pentobarbital anesthetized dogs. Recovery time and the first five cardiac cycles were examined after pacing atria and ventricles for 20, 40, and 60 seconds at four or more pacing cycle leng...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Neely BH,Urthaler F,Hageman GR

    更新日期:1985-07-01 00:00:00

  • Receptor-interacting protein kinase 3 contributes to abdominal aortic aneurysms via smooth muscle cell necrosis and inflammation.

    abstract:RATIONALE:Depletion of medial smooth muscle cell (SMC) is a major pathological characteristic of abdominal aortic aneurysm (AAA), although the mechanism by which these cells are eliminated remains incompletely understood. We reasoned that necroptosis, a recently described form of necrosis mediated by receptor-interacti...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Wang Q,Liu Z,Ren J,Morgan S,Assa C,Liu B

    更新日期:2015-02-13 00:00:00