Abstract:
RATIONALE:The development of the cardiac outflow tract (OFT) and great vessels is a complex process that involves coordinated regulation of multiple progenitor cell populations. Among these populations, neural crest cells make important contributions to OFT formation and aortic arch remodeling. Although numerous signaling pathways, including Notch, have been implicated in this process, the role of epigenetics in OFT development remains largely unexplored. OBJECTIVE:Because histone deacetylases (Hdacs) play important roles in the epigenetic regulation of mammalian development, we have investigated the function of Hdac3, a class I Hdac, during cardiac neural crest development in mouse. METHODS AND RESULTS:Using 2 neural crest drivers, Wnt1-Cre and Pax3(Cre), we show that loss of Hdac3 in neural crest results in perinatal lethality and cardiovascular abnormalities, including interrupted aortic arch type B, aortic arch hypoplasia, double-outlet right ventricle, and ventricular septal defect. Affected embryos are deficient in aortic arch artery smooth muscle during midgestation, despite intact neural crest cell migration and preserved development of other cardiac and truncal neural crest derivatives. The Hdac3-dependent block in smooth muscle differentiation is cell autonomous and is associated with downregulation of the Notch ligand Jagged1, a key driver of smooth muscle differentiation in the aortic arch arteries. CONCLUSIONS:These results indicate that Hdac3 plays a critical and specific regulatory role in the neural crest-derived smooth muscle lineage and in formation of the OFT.
journal_name
Circ Resjournal_title
Circulation researchauthors
Singh N,Trivedi CM,Lu M,Mullican SE,Lazar MA,Epstein JAdoi
10.1161/CIRCRESAHA.111.255067subject
Has Abstractpub_date
2011-11-11 00:00:00pages
1240-9issue
11eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.111.255067journal_volume
109pub_type
杂志文章abstract::To test the hypothesis that the capacity to develop left ventricular (LV) hypertrophy might diminish with advancing age, we examined the hypertrophic response to ascending aortic constriction in 3 groups of adult Fischer 344 rats (9 months, 18 months, and 22 months of age). Aortic constriction was created so that aort...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.3.337
更新日期:1987-09-01 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
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000138449.85324.c5
更新日期:2004-08-20 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.67.4.803
更新日期:1990-10-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.4.779
更新日期:1989-04-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1988-06-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh0801.089542
更新日期:2001-04-27 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.79.6.1122
更新日期:1996-12-01 00:00:00
abstract:RATIONALE:Oxidative stress is an important contributing factor in several human pathologies ranging from atherosclerosis to cancer progression; however, the mechanisms underlying tissue protection from oxidation products are poorly understood. Oxidation of membrane phospholipids, containing the polyunsaturated fatty ac...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.305925
更新日期:2015-07-31 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.176354
更新日期:2008-07-18 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.5.844
更新日期:1994-11-01 00:00:00
abstract::The effects of sodium pump inhibition produced by exposure to the cardiac glycosides, ouabain or dihydroouabain, or by reduction in extracellular potassium to 1.0 mM, on contractile state and sodium-calcium exchange were studied in primary monolayer cultures of chick embryo ventricular cells. Ouabain, 10(-6)M, dihydro...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.2.231
更新日期:1985-02-01 00:00:00
abstract::Ryanodine receptor (RyR) phosphorylation by protein kinase A (PKA) may be important in modulating resting sarcoplasmic reticulum (SR) Ca2+ release, especially in heart failure. However, clear cellular data on PKA-dependent modulation of cardiac RyRs is limited because of difficulty in distinguishing between PKA effect...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh0302.105660
更新日期:2002-02-22 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.5.1001
更新日期:1988-05-01 00:00:00
abstract::The purpose of this study was to evaluate the limitations of the double sucrose gap voltage clamp technique in the determination of tension-voltage relationships for frog atrial muscle. Tension-voltage relationships were determined under two conditions. In one case we determined both the tension response and slow inwa...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.1.106
更新日期:1976-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.86.10.1093
更新日期:2000-05-26 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.2.286
更新日期:1988-02-01 00:00:00
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
doi:10.1161/01.RES.0000059562.91384.1A
更新日期:2003-03-07 00:00:00
abstract::The dynamic interaction of simultaneously changing heart period and single vagal stimuli on atrioventricular conduction (AV interval) was quantified by subtracting the vagally induced responses of the paced heart preparation from those of the unpaced heart preparation. This difference was significantly greater (P less...
journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1977-01-01 00:00:00
abstract::During cardiac development, the epicardium is the source of multipotent mesenchymal cells, which give rise to endothelial and smooth muscle cells in coronary vessels and also, possibly, to cardiomyocytes. The aim of the present study was to determine whether stem cells are retained in the adult human and murine epicar...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.150755
更新日期:2007-12-07 00:00:00
abstract::The spatial and dynamic properties of ventricular fibrillation (VF) may be random or related to cellular electrical properties of the normal heart. Local activation intervals (AIs) in VF may depend on the local refractory period (RP), and sustained VF may require a steep action potential (AP) restitution curve. In gui...
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pub_type: 杂志文章
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更新日期:2001-03-16 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1997-10-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1983-12-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000113923.85084.C1
更新日期:2004-02-20 00:00:00
abstract::During an investigation of the effect of ryanodine on contractions in cardiac muscle, it was found that long rest periods removed all or most of the drug's effect. Therefore, we studied the kinetics of block development and recovery from block produced by low concentrations of ryanodine (1-100 pM) on the postrest cont...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.60.4.560
更新日期:1987-04-01 00:00:00
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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::We have recently characterized the promoter region of the rabbit embryonic smooth muscle myosin heavy chain (SMemb/NMHC-B) gene and identified the 15-bp sequence, designated SE1, located at -105 from the transcriptional start site as an important regulatory element for its transcriptional activity in a smooth muscle c...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.2.182
更新日期:1999-07-23 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2007-12-07 00:00:00
abstract::Cardiac alpha-adrenergic receptors mediate cellular responses to norepinephrine through an undefined series of molecular events. We examined the possibility that phosphoinositide hydrolysis was stimulated through alpha-adrenergic receptors in cardiomyocytes purified from adult rat ventricle. Phosphoinositide stores we...
journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1985-10-01 00:00:00
abstract::The SCN5A gene encodes the alpha subunit of the human heart sodium channel (hH1), which plays a critical role in cardiac excitability. Mutations of SCN5A underlie Brugada syndrome, an inherited disorder that leads to ventricular fibrillation and sudden death. This study describes changes in cellular localization and f...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1201.093270
更新日期:2001-06-22 00:00:00