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 myocytes. Transient transfection of Haras, which expresses an activated form of p21ras, effected a modest stimulation of basal hANP-chloramphenicol acetyl transferase (hANPCAT) expression. Noteworthy, the same construct inhibited both c-Jun- and Jun B-stimulated hANPCAT activity (60% and 80%, respectively). Cotransfection of a dominant-negative Ras mutant reversed this inhibition completely. The inhibitory effect was promoter selective in this system. Of those tested, only the hANP and cardiac troponin T promoters were suppressed by Ras. The inhibitory effect appears to operate through a Ras-mediated increase in c-Fos activity as evidenced by (1) the absence of additivity of the Ha-Ras- and c-Fos-mediated inhibition at higher levels of proto-oncogene expression, (2) Ras-dependent activation of c-fos gene transcription, inferred from the induction of a c-fos chloramphenicol acetyl transferase reporter (3.4-fold), and (3) reversal of Ras inhibition by a c-fos antisense oligonucleotide but not by a scrambled DNA sequence of identical base composition or the complementary sense oligonucleotide. Our findings suggest that p21tas can exert a wide range of effects on the phenotype of the cardiac ventricular myocyte. The direction that these effects take appears largely to be a function of the preexisting activation state of the cell.
journal_name
Circ Resjournal_title
Circulation researchauthors
Kovacic-Milivojevic B,Zlock DW,Gardner DGsubject
Has Abstractpub_date
1997-04-01 00:00:00pages
580-8issue
4eissn
0009-7330issn
1524-4571journal_volume
80pub_type
杂志文章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:RATIONALE:Upregulation of endothelial vascular cell adhesion molecule (VCAM)-1 and the subsequent increase in monocyte recruitment constitute critical events in atherogenesis. We have recently shown that in human coronary artery endothelial cells (HCAECs) regulated expression of VCAM-1 depends, to a significant extent,...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.213314
更新日期:2010-05-14 00:00:00
abstract::Inflammatory cell infiltration is a feature of postischemic neovascularization. However, mechanisms leading to leukocyte attraction to the site of neovascularization are still undefined. We hypothesized that the CXC chemokine receptor 3 (CXCR3) may contribute to leukocyte accumulation and subsequently to blood vessel ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000159389.55544.20
更新日期:2005-03-18 00:00:00
abstract:RATIONALE:We previously discovered several phosphorylations to the beta subunit of the mitochondrial F(1)F(o) ATP synthase complex in isolated rabbit myocytes on adenosine treatment, an agent that induces cardioprotection. The role of these phosphorylations is unknown. OBJECTIVE:The present study focuses on the functi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.214155
更新日期:2010-02-19 00:00:00
abstract:RATIONALE:Higher social integration is associated with lower cardiovascular mortality; however, whether it is associated with incident coronary heart disease (CHD), especially in women, and whether associations differ by case fatality are unclear. OBJECTIVES:This study sought to examine the associations between social...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.309443
更新日期:2017-06-09 00:00:00
abstract::Many cell types undergo apoptosis under conditions of ischemia. Little is known, however, about the molecular pathways that mediate this response. A cellular and biochemical approach to elucidate such signaling pathways was undertaken in primary cultures of cardiac myocytes, a cell type that is especially sensitive to...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.5.403
更新日期:1999-09-03 00:00:00
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
doi:10.1161/01.res.84.1.9
更新日期:1999-01-08 00:00:00
abstract::Isovolumic relaxation abnormalities have been noted in the ischemic left ventricle, but altered end-diastolic distensibility, as well as the role of right ventricular distention, is debated. Accordingly, left ventricular end-diastolic pressure and myocardial segment length were studied in the open-chest dogs with crit...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.55.2.203
更新日期:1984-08-01 00:00:00
abstract:RATIONALE:Elevations in C-reactive protein (CRP) are associated with increased cardiovascular disease risk and endothelial dysfunction. CRP antagonizes endothelial nitric oxide synthase (eNOS) through processes mediated by the IgG receptor Fcγ receptor IIB (FcγRIIB), its immunoreceptor tyrosine-based inhibitory motif, ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.254573
更新日期:2011-10-28 00:00:00
abstract::The regulation of mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK) was studied in freshly isolated adult rat heart preparations. In contrast to the situation in ventricular myocytes cultured from neonatal rat hearts, stimulation of MAPK activity by 1 mumol/L phorbol 12-myristate 13-acetate (PMA) was not c...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.5.932
更新日期:1994-11-01 00:00:00
abstract::To determine whether the attenuation in the growth capacity of myocytes in the overloaded aging heart is associated with an impairment in the activation of insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) in the stressed cells, large myocardial infarcts were produced in Fischer 344 rats at 4 and 16 month...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.4.536
更新日期:1996-04-01 00:00:00
abstract::To determine the time course of efferent sympathetic denervation after transmural myocardial infarction (TMI) and of efferent vagal denervation after transmural or nontransmural myocardial infarction (NTMI), we measured effective refractory periods (ERP) basal and apical to TMI or NTMI in secobarbital-anesthetized, op...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.6.1111
更新日期:1988-06-01 00:00:00
abstract::CD40 is a 48-kDa phosphorylated transmembrane glycoprotein belonging to the TNF receptor superfamily. CD40 has been demonstrated on a range of cell types, and it has an important role in adaptive immunity and inflammation. CD40 has recently been described on platelets but platelet activation by CD40 has not been descr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000070111.98158.6C
更新日期:2003-05-16 00:00:00
abstract::Mitochondria have long been known to play a critical role in maintaining the bioenergetic status of cells under physiological conditions. It was also recognized early in mitochondrial research that the reduction of oxygen to generate the free radical superoxide occurs at various sites in the respiratory chain and was ...
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:RATIONALE:The dramatic upregulation of αvβ3-integrin that occurs in the vasculature during tumor growth has long suggested that the endothelial expression of this molecule is an ideal target for antiangiogenic therapy to treat cancer. This discovery led to the development of small-molecule inhibitors directed against α...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.301591
更新日期:2014-01-03 00:00:00
abstract::Bradykinin relaxes arterioles on the brain's surface. This response is endothelium-dependent. The data presented here confirm the hypothesis that hydroxyl free radical mediates this response and may be the endothelium-dependent relaxing factor for bradykinin in this microvascular bed. The response to a locally applied...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.4.601
更新日期:1987-10-01 00:00:00
abstract::We have previously shown that a cryoactivatable inactive form of renin, which we have tentatively termed prorenin, occurs in human plasma. Plasma prorenin is measured by subtracting the endogenous plasma renin activity (PRA) from the total renin activity measured after cryoactivation. Cryoactivation is accomplished by...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
abstract::Bone morphogenetic protein receptor 2 (BMPR2) mutations have been linked to familial pulmonary arterial hypertension (PAH), but the molecular pathways leading to this severe pathology remain poorly characterized. We report that hypoxia, a paramount stimulus for the development of pulmonary hypertension, suppresses the...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000237021.65103.24
更新日期:2006-08-04 00:00:00
abstract::Leukocyte-derived microparticles (LMPs) may originate from neutrophils, monocytes/macrophages, and lymphocytes. They express markers from their parental cells and harbor membrane and cytoplasmic proteins as well as bioactive lipids implicated in a variety of mechanisms, maintaining or disrupting vascular homeostasis. ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.110.233403
更新日期:2012-01-20 00:00:00
abstract:RATIONALE:Cardiac myosin-binding protein-C (cMyBP-C) phosphorylation at Ser-273, Ser-282, and Ser-302 regulates myocardial contractility. In vitro and in vivo experiments suggest the nonequivalence of these sites and the potential importance of Ser-282 phosphorylation in modulating the protein's overall phosphorylation...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.242560
更新日期:2011-07-08 00:00:00
abstract::Previous studies have postulated an important role for the inwardly rectifying potassium current (I(K1)) in controlling the dynamics of electrophysiological spiral waves responsible for ventricular tachycardia and fibrillation. In this study, we developed a novel tissue model of cultured neonatal rat ventricular myocy...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.178335
更新日期:2009-02-13 00:00:00
abstract::Phospholamban is a key regulatory protein that defines diastolic function. Proinflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) can depress contractility and intracellular Ca2+ currents and transients. An alteration in phospholamban expression is a possible pathway by wh...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.4.493
更新日期:1997-10-01 00:00:00
abstract::Advances in immunosuppression have decreased the incidence of acute rejection, but the development of vasculopathy in the coronary arteries of transplants continues to limit the survival of cardiac allografts. Transplant vasculopathy has also been referred to as accelerated graft arteriosclerosis because it has featur...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000255032.33661.88
更新日期:2007-02-02 00:00:00
abstract::Previously, it was shown that the D enantiomer of isoidide dinitrate was 10-fold more potent than the L enantiomer and 10-fold less potent than glyceryl trinitrate for stimulating cyclic GMP accumulation and relaxation of isolated rat aorta. In the present study, these organic nitrates were tested for their ability to...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.4.693
更新日期:1988-10-01 00:00:00
abstract::The effects of acute renovascular hypertension on the sympathetic nervous system, regional blood flow and cardiac function were studied in conscious dogs submitted to renal artery occlusion by inflation of a cuff implanted previously around one renal artery. We then compared the alterations in plasma renin and catecho...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.47.3.356
更新日期:1980-09-01 00:00:00
abstract::We investigated the combined effectiveness of intra-aortic balloon counterpulsation and hyperosmotic mannitol (25%) on regional myocardial blood flow during acute coronary insufficiency. Cardiac output and paced heart rate were held constant in chloralose-anesthetized dogs during right heart bypass. Acute coronary ins...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.38.6.506
更新日期:1976-06-01 00:00:00
abstract::Recent studies have shown that the primary heart tube continues to grow by addition of cells from the coelomic wall. This growth occurs concomitantly with embryonic folding and formation of the coelomic cavity, making early heart formation morphologically complex. A scarcity of data on localized growth parameters furt...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.185843
更新日期:2009-01-30 00:00:00
abstract::Dimethylarginie dimethylaminohydrolase (DDAH) degrades asymmetric dimethylarginine (ADMA), an endogenous nitric oxide (NO) synthase inhibitor, and comprises 2 isoforms, DDAH1 and DDAH2. To investigate the in vivo role of DDAH2, we generated transgenic mice overexpressing DDAH2. The transgenic mice manifested reduction...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.156901
更新日期:2007-07-20 00:00:00
abstract::Human peripheral blood leukocytes, activated by phorbol myristate acetate, disrupt canine sarcoplasmic reticulum calcium transport, in vitro, by an oxygen-derived free radical mechanism. Activated leukocytes significantly depress Ca++ uptake activity and Ca++ -stimulated, Mg++ -dependent ATPase activity. The depressio...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.53.5.584
更新日期:1983-11-01 00:00:00
abstract::Previous studies have suggested that intravenous infusion of arginine vasopressin (AVP) inhibits sympathetic nerve activity (SNA) in rabbits by its action at the brainstem. This study aimed to determine, first, whether this action of AVP depended on functioning baroreflex mechanisms. The second aim was to determine th...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.5.1390
更新日期:1989-11-01 00:00:00