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














  • Reflex regulation of sympathetic activity in the spontaneously hypertensive rat.

    abstract::The influence that the pressure-sensitive receptors in the cardiovascular system have on renal nerve activity and on heart rate was compared in normotensive rats (NTR) and spontaneously hypertensive rats (SHR). The cardiovascular receptors were stimulated by raising the blood pressure (BP) with intravenous phenylephri...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Coote JH,Sato Y

    更新日期:1977-06-01 00:00:00

  • Regulation of glomerular filtration and proximal tubule reabsorption.

    abstract::In this review current hypotheses for the regulation of filtration rate and the subsequent reabsorption of that filtrate by the proximal tubule are discussed. In the rat the filtration rate is highly plasma flow dependent because of the phenomenon of filtration equilibrium. On the other hand, in man and dog filtration...

    journal_title:Circulation research

    pub_type: 杂志文章,评审


    authors: Knox FG,Cuche J-L,Ott CE,Diaz-Buxo JA,Marchand G

    更新日期:1975-06-01 00:00:00

  • Adenosine monophosphate-activated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression.

    abstract::Vascular smooth muscle cell (VSMC) proliferation is a critical event in the development and progression of vascular diseases, including atherosclerosis. We investigated whether the activation of adenosine monophosphate-activated protein kinase (AMPK) could suppress VSMC proliferation and inhibit cell cycle progression...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Igata M,Motoshima H,Tsuruzoe K,Kojima K,Matsumura T,Kondo T,Taguchi T,Nakamaru K,Yano M,Kukidome D,Matsumoto K,Toyonaga T,Asano T,Nishikawa T,Araki E

    更新日期:2005-10-14 00:00:00

  • L- and T-type Ca2+ channels in canine cardiac Purkinje cells. Single-channel demonstration of L-type Ca2+ window current.

    abstract::Canine cardiac Purkinje cells contain both L- and T-type calcium currents, yet the single Ca2+ channels have not been characterized from these cells. Additionally, previous studies have shown an overlap between the steady-state inactivation and activations curves for L-type Ca2+ currents, suggesting the presence of L-...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Shorofsky SR,January CT

    更新日期:1992-03-01 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

  • GDF11 does not rescue aging-related pathological hypertrophy.

    abstract:RATIONALE:Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-β super family of secreted factors. A recent study showed that reduced GDF11 blood levels with aging was associated with pathological cardiac hypertrophy (PCH) and restoring GDF11 to normal levels in old mice rescued PCH. ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Smith SC,Zhang X,Zhang X,Gross P,Starosta T,Mohsin S,Franti M,Gupta P,Hayes D,Myzithras M,Kahn J,Tanner J,Weldon SM,Khalil A,Guo X,Sabri A,Chen X,MacDonnell S,Houser SR

    更新日期:2015-11-06 00:00:00

  • Gene expression profiling of the forming atrioventricular node using a novel tbx3-based node-specific transgenic reporter.

    abstract::The atrioventricular (AV) node is a recurrent source of potentially life-threatening arrhythmias. Nevertheless, limited data are available on its developmental control or molecular phenotype. We used a novel AV nodal myocardium-specific reporter mouse to gain insight into the gene programs determining the formation an...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Horsthuis T,Buermans HP,Brons JF,Verkerk AO,Bakker ML,Wakker V,Clout DE,Moorman AF,'t Hoen PA,Christoffels VM

    更新日期:2009-07-02 00:00:00

  • Effects of cytosolic ATP on Ca(2+) sparks and SR Ca(2+) content in permeabilized cardiac myocytes.

    abstract::Confocal imaging was used to study the influence of cytosolic ATP on the properties of spontaneous Ca(2+) sparks in permeabilized ventricular myocytes. Cells were perfused with mock intracellular solutions containing fluo 3. Reducing [ATP] to <0.5 mmol/L decreased the frequency but increased the amplitude of spontaneo...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Yang Z,Steele DS

    更新日期:2001-09-14 00:00:00

  • Regulation of smooth muscle cell proliferation by beta-catenin/T-cell factor signaling involves modulation of cyclin D1 and p21 expression.

    abstract::We previously observed that stimulation of vascular smooth muscle cell (VSMC) proliferation with growth factors is associated with dismantling of cadherin junctions and nuclear translocation of beta-catenin. In this study we demonstrate directly that growth factors stimulate beta-catenin/T-cell factor (TCF) signaling ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Quasnichka H,Slater SC,Beeching CA,Boehm M,Sala-Newby GB,George SJ

    更新日期:2006-12-08 00:00:00

  • Formation of F2-isoprostanes during oxidation of human low-density lipoprotein and plasma by peroxynitrite.

    abstract::F2-Isoprostanes are novel bioactive prostaglandin F2-like compounds produced by nonenzymatic free radical-catalyzed peroxidation of arachidonic acid. F2-Isoprostanes are initially formed in situ on phospholipids and subsequently released. Quantification of the F2-isoprostanes has been found to represent a valuable and...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Moore KP,Darley-Usmar V,Morrow J,Roberts LJ 2nd

    更新日期:1995-08-01 00:00:00

  • The effect of hypoxia on the regional distribution of cardiac output in the dog.

    abstract::Twenty-one dogs were studied under conditions of normal oxygenation and hypoxia with the microsphere distribution method to determine the effect of arterial oxygen saturation on the regional distribution of cardiac output. The dogs were anesthetized and artifically ventilated. Cannulas were placed in the left ventricl...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Adachi H,Strauss W,Ochi H,Wagner HN Jr

    更新日期:1976-09-01 00:00:00

  • Wt1 and epicardial fate mapping.

    abstract:RATIONALE:The embryonic epicardium is a crucial cell source of the cardiac fibrous skeleton as well as of the coronary system. Genetic lineage tracing systems based on Wt1 regulatory sequences provided evidence that epicardium-derived cells also adopt a myocardial fate in the mouse. OBJECTIVE:To define the adequacy of...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Rudat C,Kispert A

    更新日期:2012-07-06 00:00:00

  • Antithrombotic Agents.

    abstract::Recent advances in our understanding of the contribution of thrombin generation to arterial thrombosis and the role of platelets in venous thrombosis have prompted new treatment paradigms. Nonetheless, bleeding remains the major side effect of such treatments spurring the quest for new antithrombotic regimens with bet...

    journal_title:Circulation research

    pub_type: 杂志文章,评审


    authors: Chan NC,Weitz JI

    更新日期:2019-02-01 00:00:00

  • Proinflammatory activation of macrophages by basic calcium phosphate crystals via protein kinase C and MAP kinase pathways: a vicious cycle of inflammation and arterial calcification?

    abstract::Basic calcium phosphate (BCP) crystal deposition underlies the development of arterial calcification. Inflammatory macrophages colocalize with BCP deposits in developing atherosclerotic lesions and in vitro can promote calcification through the release of TNF alpha. Here we have investigated whether BCP crystals can e...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Nadra I,Mason JC,Philippidis P,Florey O,Smythe CD,McCarthy GM,Landis RC,Haskard DO

    更新日期:2005-06-24 00:00:00

  • Heterogeneous changes in epimyocardial microvascular size during graded coronary stenosis. Evidence of the microvascular site for autoregulation.

    abstract::The purpose of this study was to determine the coronary microvascular sites of autoregulation. The epimyocardial coronary microcirculation was observed through an intravital microscope by stroboscopic epi-illumination in anesthetized open-chest dogs (n = 20). Aortic pressure and heart rate were held constant by an aor...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Kanatsuka H,Lamping KG,Eastham CL,Marcus ML

    更新日期:1990-02-01 00:00:00

  • Interferon-gamma induces AT(2) receptor expression in fibroblasts by Jak/STAT pathway and interferon regulatory factor-1.

    abstract::The expression of angiotensin II type 2 (AT(2)) receptor is closely associated with cell growth, differentiation, and/or injury. We examined the effect of interferon (IFN)-gamma on AT(2) receptor expression in mouse fibroblast R3T3 cells and demonstrated that IFN-gamma treatment increased the expression of AT(2) recep...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Horiuchi M,Hayashida W,Akishita M,Yamada S,Lehtonen JY,Tamura K,Daviet L,Chen YE,Hamai M,Cui TX,Iwai M,Minokoshi Y

    更新日期:2000-02-04 00:00:00

  • Phospholemman phosphorylation mediates the protein kinase C-dependent effects on Na+/K+ pump function in cardiac myocytes.

    abstract::Because phospholemman (PLM) regulates the Na(+)/K(+) pump (NKA) and is a major cardiac phosphorylation target for both protein kinase A (at Ser68) and protein kinase C (PKC) (at both Ser63 and Ser68), we evaluated whether PLM mediates the PKC-dependent regulation of NKA function and protein kinase A/PKC crosstalk in v...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Han F,Bossuyt J,Despa S,Tucker AL,Bers DM

    更新日期:2006-12-08 00:00:00

  • Sphingomyelin and other phospholipid metabolism in the rabbit atheromatous and normal aorta.

    abstract::Hypercholesterolemia induces atheroma formation, and the concentration of sphingomyelin is increased compared with that in the normal aortic intima-media. The aortic intima-media sphingomyelin concentration appears to increase exponentially with time on the cholesterol diet. Moreover, the entry rate of serum sphingomy...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Seth SK,Newman AI

    更新日期:1975-02-01 00:00:00

  • Cardiac-specific ablation of G-protein receptor kinase 2 redefines its roles in heart development and beta-adrenergic signaling.

    abstract::G-protein receptor kinase 2 (GRK2) is 1 of 7 mammalian GRKs that phosphorylate ligand-bound 7-transmembrane receptors, causing receptor uncoupling from G proteins and potentially activating non-G-protein signaling pathways. GRK2 is unique among members of the GRK family in that its genetic ablation causes embryonic le...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Matkovich SJ,Diwan A,Klanke JL,Hammer DJ,Marreez Y,Odley AM,Brunskill EW,Koch WJ,Schwartz RJ,Dorn GW 2nd

    更新日期:2006-10-27 00:00:00

  • Metabolic coupling of glutathione between mouse and quail cardiac myocytes and its protective role against oxidative stress.

    abstract::Cultured quail myocytes were much more resistant to H2O2 toxicity than cultured mouse myocytes. The intracellular concentration of glutathione ([GSH]i) and the activity of gamma-glutamylcysteine synthetase (gamma-GCS) in quail heart cells were about five and three times higher, respectively, than in mouse heart cells,...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Nakamura TY,Yamamoto I,Kanno Y,Shiba Y,Goshima K

    更新日期:1994-05-01 00:00:00

  • Relative contributions of connexins 40 and 43 to atrial impulse propagation in synthetic strands of neonatal and fetal murine cardiomyocytes.

    abstract::Atrial tissue expresses both connexin 40 (Cx40) and 43 (Cx43) proteins. To assess the relative roles of Cx40 and Cx43 in atrial electrical propagation, we synthesized cultured strands of atrial myocytes derived from mice with genetic deficiency in Cx40 or Cx43 expression and measured propagation velocity (PV) by high-...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Beauchamp P,Yamada KA,Baertschi AJ,Green K,Kanter EM,Saffitz JE,Kléber AG

    更新日期:2006-11-24 00:00:00

  • Beat-by-Beat Cardiomyocyte T-Tubule Deformation Drives Tubular Content Exchange.

    abstract:RATIONALE:The sarcolemma of cardiomyocytes contains many proteins that are essential for electromechanical function in general, and excitation-contraction coupling in particular. The distribution of these proteins is nonuniform between the bulk sarcolemmal surface and membrane invaginations known as transverse tubules ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Rog-Zielinska EA,Scardigli M,Peyronnet R,Zgierski-Johnston CM,Greiner J,Madl J,O'Toole ET,Morphew M,Hoenger A,Sacconi L,Kohl P

    更新日期:2021-01-22 00:00:00

  • Adeno-associated virus vectors for vascular gene delivery.

    abstract::A variety of delivery systems have been used to genetically modify vascular endothelial cells and smooth muscle cells (SMCs), but currently available systems suffer from either inefficient in vivo gene transfer, transient episomal vector expression, or significant immune responses and inflammation. In the present stud...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Lynch CM,Hara PS,Leonard JC,Williams JK,Dean RH,Geary RL

    更新日期:1997-04-01 00:00:00

  • Fetal blood volume responses to acute fetal hemorrhage.

    abstract::The purpose of this study was to explore the changes in fetal blood volume that occur after fetal hemorrhage. Fifteen unanesthetized, chronically catheterized fetal sheep averaging 130 +/- 3 (SD) days gestation were studied 4 to 6 (average 5) days after catheter implantation. The fetuses were hemorrhaged by continuous...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Brace RA

    更新日期:1983-06-01 00:00:00

  • Troponin I degradation and covalent complex formation accompanies myocardial ischemia/reperfusion injury.

    abstract::Selective troponin I (TnI) modification has been demonstrated to be in part responsible for the contractile dysfunction observed with myocardial ischemia/reperfusion injury. We have isolated and characterized modified TnI products in isolated rat hearts after 0, 15, or 60 minutes of ischemia followed by 45 minutes of ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: McDonough JL,Arrell DK,Van Eyk JE

    更新日期:1999-01-08 00:00:00

  • Heterogeneous behavior of the canine arterial and venous wall. Importance of the endothelium.

    abstract::Experiments were designed to determine the contribution of endothelial cells to the heterogeneous behavior of the arterial and venous wall. Rings of canine femoral, pulmonary, saphenous, and splenic arteries and veins, with and without endothelium, were mounted for isometric tension recording in Krebs-Ringer bicarbona...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: De Mey JG,Vanhoutte PM

    更新日期:1982-10-01 00:00:00

  • The relationship between ultrasonic pulsatility index and proximal arterial stenosis in a canine model.

    abstract::Although the ultrasonic pulsatility index (PI) is used as a test of arterial inflow, the relationship between proximal arterial stenosis and PI has not been fully evaluated. In a series of experiments on dogs, over 200 measurements of pressure, flow (using an indwelling electromagnetic flowmeter), and PI were made dis...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Evans DH,Barrie WW,Asher MJ,Bentley S,Bell PR

    更新日期:1980-04-01 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

  • Phosphoinositide-dependent kinase 1 and p21-activated protein kinase mediate reactive oxygen species-dependent regulation of platelet-derived growth factor-induced smooth muscle cell migration.

    abstract::Smooth muscle cell migration in response to platelet-derived growth factor (PDGF) is a key event in several vascular pathologies, including atherosclerosis and restenosis. PDGF increases intracellular levels of reactive oxygen species (ROS) in vascular smooth muscle cells (VSMCs), but the ROS sensitivity of migration ...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: Weber DS,Taniyama Y,Rocic P,Seshiah PN,Dechert MA,Gerthoffer WT,Griendling KK

    更新日期:2004-05-14 00:00:00

  • Hypoxia stimulates prostacyclin synthesis in newborn pulmonary artery endothelium by increasing cyclooxygenase-1 protein.

    abstract::In newborn lambs, pulmonary prostacyclin (PGI2) production increases acutely in response to low oxygen. We tested the hypothesis that decreased oxygenation directly stimulates PGI2 synthesis in arterial segments and cultured endothelial cells from newborn lamb intrapulmonary arteries. In segments studied at PO2 of 680...

    journal_title:Circulation research

    pub_type: 杂志文章


    authors: North AJ,Brannon TS,Wells LB,Campbell WB,Shaul PW

    更新日期:1994-07-01 00:00:00