Abstract:
RATIONALE:Myocardial infarction (MI) results in loss of cardiac myocytes in the ischemic zone of the heart, followed by fibrosis and scar formation, which diminish cardiac contractility and impede angiogenesis and repair. Myofibroblasts, a specialized cell type that switches from a fibroblast-like state to a contractile, smooth muscle-like state, are believed to be primarily responsible for fibrosis of the injured heart and other tissues, although the transcriptional mediators of fibrosis and myofibroblast activation remain poorly defined. Myocardin-related transcription factors (MRTFs) are serum response factor (SRF) cofactors that promote a smooth muscle phenotype and are emerging as components of stress-responsive signaling. OBJECTIVE:We aimed to examine the effect of MRTF-A on cardiac remodeling and fibrosis. METHODS AND RESULTS:Here, we show that MRTF-A controls the expression of a fibrotic gene program that includes genes involved in extracellular matrix production and smooth muscle cell differentiation in the heart. In MRTF-A-null mice, fibrosis and scar formation following MI or angiotensin II treatment are dramatically diminished compared with wild-type littermates. This protective effect of MRTF-A deletion is associated with a reduction in expression of fibrosis-associated genes, including collagen 1a2, a direct transcriptional target of SRF/MRTF-A. CONCLUSIONS:We conclude that MRTF-A regulates myofibroblast activation and fibrosis in response to the renin-angiotensin system and post-MI remodeling.
journal_name
Circ Resjournal_title
Circulation researchauthors
Small EM,Thatcher JE,Sutherland LB,Kinoshita H,Gerard RD,Richardson JA,Dimaio JM,Sadek H,Kuwahara K,Olson ENdoi
10.1161/CIRCRESAHA.110.223172subject
Has Abstractpub_date
2010-07-23 00:00:00pages
294-304issue
2eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.110.223172journal_volume
107pub_type
杂志文章abstract::Cardiac hypertrophy induced by thyrotoxic stress leads to an increase in the rate of force development, velocity of shortening, tension-dependent heat generation, and myosin ATPase activity. We did studies to see whether alterations in covalent phosphorylation of myofibrillar proteins correlate with these changes. The...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.48.4.498
更新日期:1981-04-01 00:00:00
abstract:RATIONALE:Innate and adaptive immune responses alter numerous homeostatic processes that are controlled by nuclear hormone receptors. NR4A1 is a nuclear receptor that is induced in vascular pathologies, where it mediates protection. OBJECTIVE:The underlying mechanisms that regulate the activity of NR4A1 during vascula...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.258814
更新日期:2012-04-13 00:00:00
abstract:RATIONALE:We previously reported that type VI collagen deposition increases in the infarcted myocardium in vivo. To date, a specific role for this nonfibrillar collagen has not been explored in the setting of myocardial infarction (MI). OBJECTIVE:To determine whether deletion of type VI collagen in an in vivo model of...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.252734
更新日期:2012-03-16 00:00:00
abstract::L-type Ca(2+) channel (LTCC) blockers, represented by amlodipine and verapamil, are widely used antihypertensive drugs that also have antiinflammatory activities. Plasminogen (Plg) is an important mediator of macrophage recruitment, and this role depends on its interaction with Plg receptors (Plg-Rs). Plg-Rs include h...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.200311
更新日期:2009-07-17 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::Recent studies in isolated cardiac tissue preparations have demonstrated the applicability of a one-dimensional difference equation model describing the global behavior of a driven nonpacemaker cell to the understanding of rate-dependent cardiac excitation. As a first approximation to providing an ionic basis to compl...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.6.1510
更新日期:1990-12-01 00:00:00
abstract::Monocyte chemoattractant protein-1 (MCP-1) stimulates the formation of a collateral circulation on arterial occlusion. The present study served to determine whether these proarteriogenic properties of MCP-1 are preserved in hyperlipidemic apolipoprotein E-deficient (apoE-/-) mice and whether it affects the systemic de...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000052313.23087.3f
更新日期:2003-02-07 00:00:00
abstract::We previously have shown that alpha-adrenergic stimulation of canine Purkinje fibers and rat ventricle decreases automaticity. Experiments on rat ventricular myocytes in tissue culture have suggested that the decrease in automaticity induced by alpha-adrenergic stimulation depends on the development of sympathetic inn...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.2.315
更新日期:1988-02-01 00:00:00
abstract::Pharmacological modulation of [K+]o accumulation and action potential changes during acute myocardial ischemia is under evaluation as a promising new antiarrhythmic and cardioprotective strategy during myocardial ischemia and reperfusion. We studied the effects of cromakalim, a K+ channel opener that activates ATP-sen...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.6.1324
更新日期:1992-12-01 00:00:00
abstract:RATIONALE:Mitochondria are key integrators of convergent intracellular signaling pathways. Two important second messengers modulated by mitochondria are calcium and reactive oxygen species. To date, coherent mechanisms describing mitochondrial integration of calcium and oxidative signaling in arterial smooth muscle are...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.306996
更新日期:2015-12-04 00:00:00
abstract::Hemodynamic shear stress elicits a rise in endothelial [Ca2+]i, which may serve as a key second messenger to regulate many flow-associated physiological and biochemical processes. In the present study, we used Mn2+ quenching of fluorescent dye Fluo3 as an assay to investigate the Ca2+ influx of rat aortic endothelial ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000054625.24468.08
更新日期:2003-02-21 00:00:00
abstract::The effect of transmural pressure on the responsiveness of vascular smooth muscle was studied using rats with chronic occlusion of one external iliac artery. The arterial pressure in the occluded leg was reduced to approximately half of that in the contralateral unoccluded leg. Helical strips from the low- and high-pr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.5.590
更新日期:1975-05-01 00:00:00
abstract::The changes in renal function produced by endogenous synthesis of prostaglandins by the kidney were evaluated by infusing sodium arachidonate, the prescursor of the prostaglandins, into one renal artery of the dog. These changes were compared with those produced by similar infusions on performed prostaglandin (PG) E2 ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.1.197
更新日期:1975-01-01 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::The global prevalence of overweight and obesity has risen substantially over the past 4 decades and is accompanied by an increasing burden of cardiovascular risk factors such as hypertension. Metabolic surgery is the most effective method to treat obesity and may further improve associated conditions. Although most re...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.118.313320
更新日期:2019-03-29 00:00:00
abstract::High affinity binding sites of angiotensin II (A II) have been characterized in rabbit renomedullary interstitial cells in tissue culture. Binding was rapid, specific, and saturable. Scatchard analysis of steady state saturation binding data at 22 degrees C indicated a single binding site with an equilibrium dissociat...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.46.6.802
更新日期:1980-06-01 00:00:00
abstract::Endothelial cells isolated from bovine aortas without prior treatment with enzymes were cultured in RPMI 1640 medium containing 17% fetal calf serum and antibiotics. The endothelial cells at confluency (7 days) were similar to endothelium in situ or to freshly isolated endothelial cells from blood vessels as seen by l...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.6.799
更新日期:1975-06-01 00:00:00
abstract::Previous studies have shown that cardiac endothelial cells release substances that influence myocardial contraction. Since PO2 is an important stimulus that modulates endothelial function, we investigated the effects of acute moderate hypoxia and reoxygenation on the release of cardioactive factors by endothelial cell...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.5.688
更新日期:1997-05-01 00:00:00
abstract:RATIONALE:Histone deacetylase (HDAC)7 is expressed in the early stages of embryonic development and may play a role in endothelial function. OBJECTIVE:This study aimed to investigate the role of HDAC7 in endothelial cell (EC) proliferation and growth and the underlying mechanism. METHODS AND RESULTS:Overexpression of...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.213165
更新日期:2010-04-16 00:00:00
abstract::Ischemia and simulated ischemic conditions induce enhanced release of norepinephrine (NE) in the brain and the heart. Although studies with neuronal preparations demonstrated a rise in [Ca2+]i under energy-depleted conditions, such release of NE in the heart appears to be predominantly Ca2+ independent. Since Ca2+ ove...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.2.179
更新日期:1997-02-01 00:00:00
abstract:RATIONALE:Yes-associated protein (YAP), the terminal effector of the Hippo signaling pathway, is crucial for regulating embryonic cardiomyocyte proliferation. OBJECTIVE:We hypothesized that YAP activation after myocardial infarction (MI) would preserve cardiac function and improve survival. METHODS AND RESULTS:We use...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.303632
更新日期:2014-07-18 00:00:00
abstract::We have previously demonstrated that urokinase-type plasminogen activator (uPA) is highly expressed in the aneurysmal segment of the abdominal aorta (AAA) in apolipoprotein E-deficient (apoE-/-) mice treated with angiotensin II (Ang II). In the present study, we tested the hypothesis that uPA is essential for AAA form...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000061571.49375.E1
更新日期:2003-03-21 00:00:00
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
doi:10.1161/01.res.46.4.470
更新日期:1980-04-01 00:00:00
abstract:RATIONALE:Although PSA (prostate-specific antigen)-a tumor marker for prostate cancer-has been reported to be associated with cardiovascular disease (CVD) risk factors, studies on the association of PSA with subclinical and clinical CVD remain limited. OBJECTIVE:We examined the association of total serum PSA within th...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.313413
更新日期:2019-05-10 00:00:00
abstract::We performed experiments to determine whether or not acetylcholine exerts a prejunctional inhibitory effect on adrenergic neurotransmission in the human blood vessel wall. Rings of human greater saphenous veins were prepared 2 to 15 hours after death and mounted for isometric tension recording in organ chambers filled...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.49.2.337
更新日期:1981-08-01 00:00:00
abstract::The synthesis of an angiotensin II (A II) antagonist, sarcosyl1-cysteinyl(S-methyl)8-angiotensin II [Sar1-Cys(Me)8-A II], showing partial organ selectivity and properties of a noncompetitive antagonist, is described. The compound was found to be an extremely potent antagonist on vascular smooth muscle both in vitro (p...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.46.5.720
更新日期:1980-05-01 00:00:00
abstract::In urethane-anesthetized rats, electrophysiological recordings of spontaneously active neurons in the vasopressor area of the rostral ventrolateral medulla were analyzed for participation in cardiovascular regulation. A total of 138 units were found which were inhibited by transient increases in mean arterial pressure...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.3.359
更新日期:1985-03-01 00:00:00
abstract::Cardiac allograft vasculopathy (CAV) continues to be a major cause of late graft failure after cardiac transplantation. We have demonstrated that Rho-kinase, an effector of the small GTPase Rho, plays an important role in the pathogenesis of arteriosclerosis. In this study, we examined whether the Rho-kinase-mediated ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000107196.21335.2B
更新日期:2004-01-09 00:00:00
abstract::We studied the time-dependent changes in the response of heart rate (sinus cycle length) to 30-second trains of vagal stimulation (8 Hz), repeated every 2 minutes, in canine neonates aged 7.1 +/- 2.5 (mean +/- SD) days. The first vagal train prolonged the sinus cycle length by 58 +/- 35%, but the response was attenuat...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.2.406
更新日期:1991-08-01 00:00:00
abstract::We stimulated the aortic chemoreceptors in dogs that were anesthetized with chloralose and artificially ventilated by perfusing the isolated aortic arch with venous blood. Inotropic responses were determined by measuring the maximum rate of change of left ventricular pressure (dP/dt max) with aortic pressure and heart...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.46.1.77
更新日期:1980-01-01 00:00:00