Abstract:
:Transformer splicing regulatory proteins determine the sexually dimorphic traits of Drosophila. The role of the vertebrate homologs of Tra-2 in phenotypic specification is undefined. We are using the alternative splicing of the MYPT1 E23 exon as a model for the study of smooth muscle diversification into fast and slow contractile phenotypes. Tra2beta mRNA and protein is expressed at up to 10-fold higher levels in fast smooth muscle tissues such as the rat portal vein and small mesenteric artery, in which E23 is spliced, as compared to the slow smooth muscle tissues of the large arteries and veins, in which E23 is skipped. Tra2beta is upregulated up to 10-fold concordant with the initiation of E23 splicing as the rat portal vein and avian gizzard implement the fast program of gene expression in the perinatal period. In disease models such as portal hypertension and mesenteric artery high/low flow, the portal vein and first order mesenteric artery dynamically downregulate Tra2beta concordant with a shift to E23 skipping and the slow program of gene expression. Tra2beta binds to a highly conserved sequence within E23 and transactivates its splicing in vitro and in vivo; this is abolished with mutation or deletion of this sequence. RNA interference-mediated knockdown of Tra2beta markedly reduces E23 splicing. We propose that Tra2beta has been conserved through evolution and redeployed for the specification of the fast smooth muscle phenotype and may serve as a novel nodal point for the investigation of this process in developmental and disease models.
journal_name
Circ Resjournal_title
Circulation researchauthors
Shukla S,Fisher SAdoi
10.1161/CIRCRESAHA.108.178384subject
Has Abstractpub_date
2008-08-29 00:00:00pages
485-92issue
5eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.108.178384journal_volume
103pub_type
杂志文章abstract::Many indices have been proposed to describee the diastolic pressure-volume curve mathematically and permit quantification of the elastic properties of the myocardium itself in hopes that changes in the muscle caused by disease would b.e reflected in the diastolic pressure-volume curve. To date, none of the proposed in...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.6.772
更新日期:1976-12-01 00:00:00
abstract::The mechanism(s) by which mutations in sarcomeric proteins cause hypertrophic cardiomyopathy (HCM) remains unknown. A leading hypothesis proposes that mutant sarcomeric proteins impair cardiac myocyte contractility, providing an impetus for compensatory hypertrophy. To test this hypothesis, we determined the impact of...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.1.76
更新日期:1997-07-01 00:00:00
abstract::Patients with diabetes mellitus have >2× the risk for developing heart failure (HF; HF with reduced ejection fraction and HF with preserved ejection fraction). Cardiovascular outcomes, hospitalization, and prognosis are worse for patients with diabetes mellitus relative to those without. Beyond the structural and func...
journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2019-01-04 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.315786
更新日期:2019-10-25 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.res.65.2.237
更新日期:1989-08-01 00:00:00
abstract::The contractile response of the aged adult heart to beta-adrenergic stimulation is known to be reduced compared with the young adult heart. Since endogenous adenosine exerts an antiadrenergic action in the heart, this study was undertaken to determine if the basal endogenous level of myocardial adenosine increases wit...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.5.1381
更新日期:1990-05-01 00:00:00
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 contractil...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.223172
更新日期:2010-07-23 00:00:00
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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
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.307647
更新日期:2016-04-01 00:00:00
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journal_title:Circulation research
pub_type: 临床试验,杂志文章
doi:10.1161/CIRCRESAHA.114.302791
更新日期:2014-01-17 00:00:00
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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::In response to hypoxia and reoxygenation, mammalian cells are known to express a variety of genes to adapt to these external stresses or lead to further cell damage. We investigated the intracellular signaling cascades in cultured rat cardiac myocytes subjected to hypoxia followed by reoxygenation (hypoxia/reoxygenati...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.1.82
更新日期:1996-01-01 00:00:00
abstract::The solid angle theory has long been applied to the interpretation of the ECG; however, quantitative evaluation of its applicability has been minimal. We applied solid angle analysis to the interpretation of the TQ-ST deflection during acute ischemia. Five anesthetized pigs were studied 1--3 hours after coronary occlu...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.43.6.879
更新日期:1978-12-01 00:00:00
abstract::We have previously studied the relation between long-chain fatty acid and pyruvate metabolism in reperfused myocardium and noted a rapid return of fatty acid oxidation to at least preischemic values accompanied by a marked decrease in pyruvate oxidation. The purpose of the present report is to further characterize car...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.4.1094
更新日期:1989-10-01 00:00:00
abstract::Adipose tissue (AT) can accumulate macrophages and secrete several inflammatory mediators. Despite its pivotal role in the progression of chronic inflammatory processes such as atherosclerosis, the adaptive role of immunity in obesity remains poorly explored. Visceral AT of diet-induced obese C57BL/6 mice had higher n...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.177105
更新日期:2008-08-29 00:00:00
abstract::Despite the absence of a systematic development plan, β-blockers have reached the top tier of medical therapies for chronic heart failure. The successful outcome was due to the many dedicated investigators who produced, over a 30-year period, increasing evidence that β-blocking agents should or actually did improve th...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.245092
更新日期:2011-10-28 00:00:00
abstract::Lipid rafts are discrete membrane subdomains rich in sphingolipids and cholesterol. In ventricular myocytes a function of caveolae, a type of lipid rafts, is to concentrate in close proximity several proteins of the beta-adrenergic transduction pathway. We have investigated the subcellular localization of HCN4 channel...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000127621.54132.AE
更新日期:2004-05-28 00:00:00
abstract::The present study was undertaken to determine the mechanism of neointima formation in rabbit arteries subjected to extensive endothelial desquamation. Endothelial cells were selectively removed from the abdominal aorta by passing an inflated balloon catheter through the vessel. The healing response was then studied se...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.1.58
更新日期:1975-01-01 00:00:00
abstract::This review considers critically the evidence for the involvement of mediators of innate and acquired immunity in various stages of atherosclerosis. Rapidly mobilized arms of innate immunity, including phagocytic leukocytes, complement, and proinflammatory cytokines, contribute to atherogenesis. In addition, adaptive ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.res.0000029784.15893.10
更新日期:2002-08-23 00:00:00
abstract::As early as the 4th embryonic day, the ventricle of the chick embryo responded to isoproterenol (Iso) with an increase in the force of contraction; at all ages studied, this positive inotropic effect was accompanied by an increased rate of tension development. There was a transient, 10-fold decrease in the sensitivity...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.48.2.245
更新日期:1981-02-01 00:00:00
abstract::Over the last 4 decades, heart transplantation (HTx) has evolved as a mainstream therapy for heart failure. Approximately half of patients needing HTx have organ failure consequent to atherosclerosis. Despite advances in immunosuppressive drugs, long-term success of HTx is limited by the development of a particular ty...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000246086.93555.f3
更新日期:2006-10-13 00:00:00
abstract::The effect of chronic therapy with quinapril on the temporal progression of left ventricular failure and survival was assessed in the CHF 146 cardiomyopathic (CM) hamster, which is an idiopathic model of congestive heart failure. Age-matched Golden Syrian (GS) hamsters served as normal controls. Quinapril was administ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.5.1302
更新日期:1991-05-01 00:00:00
abstract::Proliferation of vascular smooth muscle cells (VSMC) is a primary cause of vascular disorders and is associated with major alterations in Ca2+ handling supported by loss of the sarco/endoplasmic reticulum calcium ATPase, SERCA2a. To determine the importance of SERCA2a in neointima formation, we have prevented loss of ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000180663.42594.aa
更新日期:2005-09-02 00:00:00
abstract::In recent year, increasing evidence suggests that noncoding RNAs play important roles in the regulation of tissue homeostasis and pathophysiological conditions. Besides small noncoding RNAs (eg, microRNAs), >200-nucleotide long transcripts, namely long noncoding RNAs (lncRNAs), can interfere with gene expressions and ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.302521
更新日期:2015-02-13 00:00:00
abstract::Postnatal development of the mammalian heart is associated with changes in the population of isoforms of the thin filament proteins. We correlated the change in thin filament proteins, which occur in rabbit hearts between 5 days and 22 days of age, with changes in Ca2+ dependence of myofibrillar ATPase activity, force...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.5.1204
更新日期:1990-05-01 00:00:00
abstract:RATIONALE:Shear stress (SS) has an established role in atherosclerotic plaque localization, but how it exerts its protective effect is not fully understood. OBJECTIVE:To test the hypothesis that SS may downregulate angiotensin type 1 receptors (AT(1)Rs). Angiotensin II has been shown to be proinflammatory and to promo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.204040
更新日期:2009-10-23 00:00:00
abstract::Matrix metalloproteinases (MMPs) and, in particular, MMP-9 are important for smooth muscle cell (SMC) migration into the intima. In this study, we sought to determine whether MMP-9 is critical for SMC migration and for the formation of a neointima by using mice in which the gene was deleted (MMP-9(-/-) mice). A denudi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000040420.17366.2e
更新日期:2002-11-01 00:00:00
abstract::We tested the hypothesis that activation of transient receptor potential vanilloid type-1 (TRPV1) by capsaicin prevents adipogenesis. TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans were detected by immunoblotting and quantitative real-time RT-PCR. The effect of TRPV1 on cytosol...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000262653.84850.8b
更新日期:2007-04-13 00:00:00
abstract::The effects of prostaglandin E2 (PGE2) indomethacin, and reserpine were evaluated in the rabbit renal vascular bed in situ under conditions of controlled blood flow. Intrarenal infusion of PGE2, 0.03 and 0.3 microgram/min, decreased responses to renal nerve stimulation, intra-arterial norepinephrine, and angiotensin. ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.41.2.172
更新日期:1977-08-01 00:00:00
abstract::Cation channels activated by Ca(2+) store depletion have been proposed to mediate Ca(2+) influx in vascular smooth muscle cells. The aim of this study was to determine if store-operated channels have a functional role in pulmonary artery smooth muscle cells (PASMCs). In intact rat pulmonary artery rings, cyclopiazonic...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh2201.100315
更新日期:2001-11-09 00:00:00