Abstract:
RATIONALE:Mammalian cardiomyocytes withdraw from the cell cycle during early postnatal development, which significantly limits the capacity of the adult mammalian heart to regenerate after injury. The regulatory mechanisms that govern cardiomyocyte cell cycle withdrawal and binucleation are poorly understood. OBJECTIVE:Given the potential of microRNAs (miRNAs) to influence large gene networks and modify complex developmental and disease phenotypes, we searched for miRNAs that were regulated during the postnatal switch to terminal differentiation. METHODS AND RESULTS:Microarray analysis revealed subsets of miRNAs that were upregulated or downregulated in cardiac ventricles from mice at 1 and 10 days of age (P1 and P10). Interestingly, miR-195 (a member of the miR-15 family) was the most highly upregulated miRNA during this period, with expression levels almost 6-fold higher in P10 ventricles relative to P1. Precocious overexpression of miR-195 in the embryonic heart was associated with ventricular hypoplasia and ventricular septal defects in β-myosin heavy chain-miR-195 transgenic mice. Using global gene profiling and argonaute-2 immunoprecipitation approaches, we showed that miR-195 regulates the expression of a number of cell cycle genes, including checkpoint kinase 1 (Chek1), which we identified as a highly conserved direct target of miR-195. Finally, we demonstrated that knockdown of the miR-15 family in neonatal mice with locked nucleic acid-modified anti-miRNAs was associated with an increased number of mitotic cardiomyocytes and derepression of Chek1. CONCLUSIONS:These findings suggest that upregulation of the miR-15 family during the neonatal period may be an important regulatory mechanism governing cardiomyocyte cell cycle withdrawal and binucleation.
journal_name
Circ Resjournal_title
Circulation researchauthors
Porrello ER,Johnson BA,Aurora AB,Simpson E,Nam YJ,Matkovich SJ,Dorn GW 2nd,van Rooij E,Olson ENdoi
10.1161/CIRCRESAHA.111.248880subject
Has Abstractpub_date
2011-09-02 00:00:00pages
670-9issue
6eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.111.248880journal_volume
109pub_type
杂志文章abstract::Acetylcholine (ACh) evokes the conduction of vasodilation along resistance microvessels. However, it is not known which cell layer (endothelium or smooth muscle) serves as the conduction pathway. In isolated, cannulated feed arteries ( approximately 70 microm in diameter at 75 mm Hg; length approximately 4 mm) of the ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.1.94
更新日期:2000-01-07 00:00:00
abstract::Vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic and uremic patients. Because of the correlation of hyperphosphatemia and vascular calcification, the ability of extracellular inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC) culture mineralizat...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.7.e10
更新日期:2000-09-29 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::Nonischemic dilated cardiomyopathy (DCM) often has a genetic pathogenesis. Because of the large number of genes and alleles attributed to DCM, comprehensive genetic testing encompasses ever-increasing gene panels. Genetic diagnosis can help predict prognosis, especially with regard to arrhythmia risk for certain subty...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.309396
更新日期:2017-09-15 00:00:00
abstract::p21ras is a potent regulator of myogenic cell growth and differentiation. It has been implicated as playing a major role in the genesis of cardiac hypertrophy. We examined the effect of Ras overexpression on human atrial natriuretic peptide (hANP) gene expression, a marker of hypertrophy, in neonatal rat ventricular m...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::The focal pattern of atherosclerotic lesions in arterial vessels suggests that local blood flow patterns are important factors in atherosclerosis. Although disturbed flows in the branches and curved regions are proatherogenic, laminar flows in the straight parts are atheroprotective. Results from in vitro studies on c...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.res.0000038487.19924.18
更新日期:2002-11-01 00:00:00
abstract::Structure/function analysis shows that the carboxyl terminal (CT) domain of connexin43 (Cx43) is essential for the chemical regulation of cell-cell communication. Of particular interest is the region between amino acids 260 and 300. Structural preservation of this region is essential for acidification-induced uncoupli...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.82.9.929
更新日期:1998-05-18 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
doi:10.1161/01.res.40.1.81
更新日期:1977-01-01 00:00:00
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
doi:10.1161/CIRCRESAHA.116.303790
更新日期:2015-04-10 00:00:00
abstract::Understanding the molecular interactions among components of cardiac Z-discs and their role in signaling has become pivotal in explaining long- and short-term regulation of cardiac function. In striated muscle, the ends of the thin filaments from opposing sarcomeres overlap and are cross-linked by an elaborate array o...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000116143.74830.A9
更新日期:2004-02-20 00:00:00
abstract::A period of prolonged vasodilation follows flow-restricted exercise of skeletal muscle. We tested the hypothesis that adenosine participates in mediating this vascular response. Vascularly isolated, anterior calf muscles of anesthetized dogs were stimulated to contract at a rate of 4 twitches/sec. Blood flow was held ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.44.6.759
更新日期:1979-06-01 00:00:00
abstract:RATIONALE:Lymphatic vessels in the respiratory tract normally mature into a functional network during the neonatal period, but under some pathological conditions they can grow as enlarged, dilated sacs that result in the potentially lethal condition of pulmonary lymphangiectasia. OBJECTIVE:We sought to determine wheth...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.303119
更新日期:2014-02-28 00:00:00
abstract::Abnormalities of myocardial gap junction-mediated cell coupling have been implicated in cardiac arrhythmogenesis. The potential role of gap junctional dysfunction in the generation of reperfusion-induced arrhythmias is uncertain. The purpose of this study was to measure the effects of myocardial ischemia and reperfusi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.1.127
更新日期:1992-07-01 00:00:00
abstract::Patients with severe heart failure are at high risk of sudden cardiac death. In the majority of these patients, sudden cardiac death is thought to be due to ventricular tachyarrhythmias. Alterations of the electric properties of single myocytes in heart failure may favor the occurrence of ventricular arrhythmias in th...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.82.11.1206
更新日期:1998-06-15 00:00:00
abstract::To determine whether calcium channel agonists and antagonists bind to distinct pharmacologically active sites, the binding of dihydropyridine calcium channel agonists and antagonists was related to calcium flux and contractile state in primary monolayer cultures of spontaneously contracting chick embryo ventricular ce...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.60.5.683
更新日期:1987-05-01 00:00:00
abstract::Activity was recorded from physiologically identified baroreceptor or chemoreceptor fibers in carotid sinus nerves of urethane-anesthetized spontaneously breathing rabbits. A carotid sinus area was vascularly isolated so that carotid sinus pressure and perfusion medium (Locke's solution or rabbit blood) could be contr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.6.1608
更新日期:1991-12-01 00:00:00
abstract::Voltage-gated K(+) channels (Kv) play a critical role in regulating arterial tone by modulating the membrane potential of vascular smooth muscle cells. Our previous work demonstrated that the dominant 4-aminopyridine (4-AP)-sensitive, delayed rectifier Kv current of rabbit portal vein (RPV) myocytes demonstrates simil...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh2301.100817
更新日期:2001-11-23 00:00:00
abstract:RATIONALE:Although the health effects of beta carotene have been studied extensively, a systematic examination of serum concentrations and long-term mortality, including cardiovascular disease mortality, has not been reported. OBJECTIVE:Explore whether serum beta carotene is associated with overall and cause-specific ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.313409
更新日期:2018-12-07 00:00:00
abstract:RATIONALE:In ventricular myocytes of large mammals with low T-tubule density, a significant number of ryanodine receptors (RyRs) are not coupled to the sarcolemma; cardiac remodeling increases noncoupled RyRs. OBJECTIVE:Our aim was to test the hypothesis that coupled and noncoupled RyRs have distinct microdomain-depen...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.113.301896
更新日期:2013-11-08 00:00:00
abstract::Angiotensin-converting enzyme (ACE) activity in the guinea pig fetal-placental unit was assessed at the different oxygen tensions found in utero, during labor, and at birth. To determine fetal-placental ACE activity, we separately perfused in situ term guinea pig fetuses and their placentas via the umbilical vessels u...
journal_title:Circulation research
pub_type: 杂志文章,收录出版
doi:10.1161/01.res.48.2.286
更新日期:1981-02-01 00:00:00
abstract::First-generation, E1-deleted adenoviral vectors (E1-AV) can transduce the vascular endothelium with high efficiency, but their use is limited by the resulting acute endothelial injury and the long-term development of intimal hyperplasia. To reduce the impact of viral proteins on the gene-modified cells, a second-gener...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh0901.090926
更新日期:2001-05-11 00:00:00
abstract::The hypothesis that alpha-adrenergic coronary vasoconstriction helps maintain a uniform transmural distribution of myocardial blood flow during exercise was tested in dogs. Carotid artery loops were surgically constructed and a splenectomy performed three weeks prior to study. On the day of study, the dog was anesthet...
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:RATIONALE:Human clinical trials using type 1 angiotensin (AT(1)) receptor antagonists indicate that angiotensin II is a critical mediator of cardiovascular and renal disease. However, recent studies have suggested that individual tissue pools of AT(1) receptors may have divergent effects on target organ damage in hyper...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.261768
更新日期:2012-06-08 00:00:00
abstract::We studied baroreceptor function in dogs before and after surgical repair of coarctation of the aorta by direct recording of multifiber carotid sinus (CS) nerve activity (NA) during alteration of pulsatile arterial pressure with systemic phenylephrine and nitroprusside, and during static pressure changes using a CS po...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.48.3.365
更新日期:1981-03-01 00:00:00
abstract:RATIONALE:Inhibition of glycogen synthase kinase-3 (GSK-3) protects the heart during ischemia/reperfusion (I/R), yet the underlying mechanisms of cardioprotection afforded by beta isoform-specific inhibition GSK-3 remain to be elucidated. OBJECTIVE:We studied the molecular mechanism mediating the effect of GSK-3β acti...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.249532
更新日期:2011-08-19 00:00:00
abstract::We studied product inhibition of the actin-activated ATPase of myosin subfragment-1 (S-1) from the three types of muscle tissue: skeletal, cardiac, and smooth. Increasing levels of [MgADP] in the 0-1-mM range caused significant inhibition of the actin-activated MgATPase activity of cardiac and gizzard but not skeletal...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.5.1067
更新日期:1992-11-01 00:00:00
abstract::The impact of vanadate on the Na,K-ATPase system in the vascular smooth muscle cell is poorly understood. The present study describes the kinetics of the effect of vanadate on Na,K-ATPase and the Na-K pump in in vitro grown rat VSMC's. Vanadate interaction with the Na,K-ATPase system in vascular smooth muscle cells wa...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.53.2.186
更新日期:1983-08-01 00:00:00
abstract:RATIONALE:Post-myocardial infarction ventricular remodeling is associated with the expression of a variety of factors including S100B that can potentially modulate myocyte apoptosis. OBJECTIVE:This study was undertaken to investigate the expression and function of S100B and its receptor, the receptor for advanced glyc...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.195834
更新日期:2010-01-08 00:00:00
abstract:RATIONALE:Specialized pro-resolving mediators (SPM-lipoxins, resolvins, protectins, and maresins) are produced via the enzymatic conversion of essential fatty acids, including the omega-3 fatty acids docosahexaenoic acid and n-3 docosapentaenoic acid. These mediators exert potent leukocyte directed actions and control ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.315506
更新日期:2020-01-03 00:00:00
abstract:RATIONALE:Thousands of mutations across >50 genes have been implicated in inherited cardiomyopathies. However, options for sequencing this rapidly evolving gene set are limited because many sequencing services and off-the-shelf kits suffer from slow turnaround, inefficient capture of genomic DNA, and high cost. Further...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.306723
更新日期:2015-09-11 00:00:00