Abstract:
:We recently showed that the transient expression of a hemagglutinin (HA) epitope-tagged, constitutively active mutant of the G protein alpha(q) subunit (HAalpha(q)*) in the hearts of transgenic mice is sufficient to induce cardiac hypertrophy and dilatation that continue to progress after HAalpha(q)* protein becomes undetectable. We demonstrated that the activity of phospholipase Cbeta, the immediate downstream target of activated Galpha(q), is increased at 2 weeks, when HAalpha(q)* is expressed, but also at 10 weeks, when HAalpha(q)* is no longer detectable. This observation suggested that the transient HAalpha(q)* expression causes multiple, persistent changes in cellular signaling pathways. We now demonstrate changes in the level, activity, or both of several signaling components, including changes in the amount and hormone responsiveness of phospholipase Cbeta enzymes, in the basal level of diacylglycerol (which predominantly reflects activation of phospholipase D), in the amount or distribution of protein kinase C (PKC) isoforms (PKCalpha, PKCdelta, and PKCepsilon), and in the amount of several endogenous G proteins. These changes vary depending on the isoform of the signaling molecule, the chamber in which it is expressed, and the presence or absence of HAalpha(q)*. Our results suggest that a network of linked signaling functions determines the development of hypertrophy. They also suggest that atria and ventricles represent different signaling domains. It is likely that such changes occur in other model systems in which the activity of a single signaling component is increased, either due to an activating mutation or due to overexpression of the wild type.
journal_name
Circ Resjournal_title
Circulation researchauthors
Mende U,Kagen A,Meister M,Neer EJdoi
10.1161/01.res.85.11.1085subject
Has Abstractpub_date
1999-11-26 00:00:00pages
1085-91issue
11eissn
0009-7330issn
1524-4571journal_volume
85pub_type
杂志文章abstract::Atherosclerotic plaque rupture is the main cause of coronary thrombosis and myocardial infarcts. Currently, there is no animal model of plaque disruption. We have developed a rabbit model in which an atherosclerotic plaque can be ruptured at will after an inflatable balloon becomes embedded into the plaque. Furthermor...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.7.705
更新日期:1998-10-05 00:00:00
abstract:RATIONALE:Hypoxia followed by reoxygenation promotes inflammation by activating nuclear factor κB transcription factors in endothelial cells (ECs). This process involves modification of the signaling intermediary tumor necrosis factor receptor-associated factor 6 with polyubiquitin chains. Thus, cellular mechanisms tha...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.300119
更新日期:2013-06-07 00:00:00
abstract:RATIONALE:Anti-inflammatory and vascular protective actions of adiponectin are well recognized. However, many fundamental questions remain unanswered. OBJECTIVE:The current study attempted to identify the adiponectin receptor subtype responsible for adiponectin's vascular protective action and investigate the role of ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.302439
更新日期:2014-02-28 00:00:00
abstract::Despite intense interest in understanding the differentiation of vascular smooth muscle, very little is known about the cellular and molecular mechanisms that control differentiation of this cell type. Progress in this field has been hampered by the lack of an inducible in vitro system for study of the early steps of ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.5.742
更新日期:1995-05-01 00:00:00
abstract::In 26 Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intravenous infusions of norepinephrine or angiotensin II. Regardless of whether renal perfusion pressure (AP) was permitted to increase, both...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.37.1.101
更新日期:1975-07-01 00:00:00
abstract::Endothelin-1 (ET-1) and endothelin-3 (ET-3) produced positive inotropic effects on electrically stimulated left atria and increased the frequency of spontaneously beating right atria of adult rats. The potency of the inotropic effect of ET-1 was greater than that of ET-3, but the potencies of the chronotropic effects ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.4.918
更新日期:1991-10-01 00:00:00
abstract:RATIONALE:Monocyte infiltration into the subintimal space and its intracellular lipid accumulation are the most prominent features of atherosclerosis. To understand the pathophysiology of atherosclerotic disease, we need to understand the characteristics of lipid-laden foamy macrophages in the subintimal space during a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.312804
更新日期:2018-10-26 00:00:00
abstract::Heart failure is associated with death of cardiomyocytes leading to loss of contractility. Previous studies using membrane-targeted Akt (myristolated-Akt), an enzyme involved in antiapoptotic signaling, showed inhibition of cell death and prevention of pathogenesis induced by cardiomyopathic stimuli. However, recent s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000124394.01180.BE
更新日期:2004-04-16 00:00:00
abstract::We designed this study to test the hypothesis that in acute mitral regurgitation the mitral regurgitant area (MRA) is a dynamic quantity which varies with the time variation of ventricular volume. Mitral insufficiency was created in five open-chest dogs in which a portion of the anterior leaflet was excised. Phasic ao...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.45.5.677
更新日期:1979-11-01 00:00:00
abstract:RATIONALE:Allogeneic mesenchymal precursor cells (MPCs) have been effective in large animal models of ischemic and nonischemic heart failure (HF). OBJECTIVE:To evaluate the feasibility and safety of 3 doses (25, 75, or 150 million cells) of immunoselected allogeneic MPCs in chronic HF patients in a phase 2 trial. MET...
journal_title:Circulation research
pub_type: 杂志文章,随机对照试验
doi:10.1161/CIRCRESAHA.115.306332
更新日期:2015-08-28 00:00:00
abstract::Fibrinopeptide A (FPA) levels were measured in a group of 130 controls and patients with various types of primary hyperlipidemia to investigate whether an increased steady state level of thrombin activity is present in hyperlipidemic patients. In a subset of 56 subjects, levels of clotting factors II, VII, and X were ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.45.3.347
更新日期:1979-09-01 00:00:00
abstract::The hallmark of most cardiac diseases is the progressive loss of cardiomyocytes. In the perinatal period, cardiomyocytes still proliferate, and the heart shows the capacity to regenerate upon injury. In the adult heart, however, the actual rate of cardiomyocyte renewal is too low to efficiently counteract substantial ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.119.315408
更新日期:2020-02-14 00:00:00
abstract::Heparin inhibits the development of intimal thickening after carotid injury in the rat; however, the specific cellular events responsible for this effect have not been defined. In this study, smooth muscle cell growth fraction and migration into the intima were quantitatively measured in heparin-treated animals. All r...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.6.839
更新日期:1986-06-01 00:00:00
abstract::Extracellular ATP plays an important role in the regulation of prostacyclin and nitric oxide release from vascular endothelial cells. These cellular responses to ATP are generally attributed to the stimulation of the P2y subtype of P2 purinergic receptors. However, it has recently been suggested that two types of ATP ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.3.504
更新日期:1993-03-01 00:00:00
abstract:RATIONALE:Clinical studies have shown that Sirt3 (Sirtuin 3) expression declines by 40% by 65 years of age paralleling the increased incidence of hypertension and metabolic conditions further inactivate Sirt3 because of increased NADH (nicotinamide adenine dinucleotide, reduced form) and acetyl-CoA levels. Sirt3 impair...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.310933
更新日期:2017-08-18 00:00:00
abstract::To investigate the regulation of the actomyosin crossbridge cycle in cardiac muscles, the effects of ATP, ADP, Pi, and creatine phosphate (CP) on the rate of force redevelopment (ktr) were measured. We report that CP is a primary determinant in controlling the actomyosin crossbridge cycling kinetics of cardiac muscles...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000080536.06932.E3
更新日期:2003-07-11 00:00:00
abstract:RATIONALE:Lipoprotein(a) [Lp(a)] is a highly atherogenic low-density lipoprotein-like particle characterized by the presence of apoprotein(a) [apo(a)] bound to apolipoprotein B. Proprotein convertase subtilisin/kexin type 9 (PCSK9) selectively binds low-density lipoprotein; we hypothesized that it can also be associate...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.308811
更新日期:2016-06-24 00:00:00
abstract::One of the major manifestations of obesity is increased production of the adipocyte-derived 16-kDa peptide leptin, which is also elevated in heart disease, including congestive heart failure. However, whether leptin can directly alter the cardiac phenotype is not known. We therefore studied the effect of leptin as a p...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000089255.37804.72
更新日期:2003-08-22 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::It is known that branching strands of cardiac tissue can form a substrate for very slow conduction. The branches slow conduction by acting as current loads drawing depolarizing current from the main strand ("pull" effect). It has been suggested that, upon depolarization of the branches, they become current sources rei...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh2101.098442
更新日期:2001-10-26 00:00:00
abstract::In the first 4 hours after occlusion of the anterior septal coronary artery, 18 dogs developed bundle branch block, heart block, or both. The hearts were then excised, and preparations were dissected to expose the His bundle and the bundle branches, which were superfused with modified Tyrode's solution at 37 degrees C...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.3.444
更新日期:1975-03-01 00:00:00
abstract::The circulatory effects associated with lifelong plasma atrial natriuretic factor (ANF) elevation were examined by generating transgenic mice, which constitutively express a fusion gene consisting of the transthyretin promoter and the ANF structural gene. These mice have chronically elevated ANF levels as compared wit...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.4.747
更新日期:1994-04-01 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::The purpose of these studies was to evaluate cardiovascular structural and functional changes in a model of hypertension-induced myocardial hypertrophy in which vasodilator therapy decreased blood pressure to normal levels. Thus, we determined the separate contributions of hypertension and hypertrophy on myocardial an...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.6.1127
更新日期:1989-06-01 00:00:00
abstract::The transcriptional regulation of cardiovascular development requires precise spatiotemporal control of gene expression, and heterozygous mutations of transcription factors have frequently been implicated in human cardiovascular malformations. A novel mechanism involving posttranscriptional regulation by small, noncod...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.108.192872
更新日期:2009-03-27 00:00:00
abstract::The hypothesis that neurally mediated coronary vasodilation occurs as part of the carotid baroreceptor reflex was investigated. The left main coronary artery was cannulated and perfused at constant pressure (100 mm Hg) in closed-chest, chloralose-anesthetized dogs. The heart was paced at a constant rate between 60 and...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.4.486
更新日期:1985-04-01 00:00:00
abstract::Transgenic mice overexpressing the calcium binding protein, S100A4/Mts1, occasionally develop severe pulmonary vascular obstructive disease. To understand what underlies this propensity, we compared the pulmonary vascular hemodynamic and structural features of S100A4/Mts1 with control C57Bl/6 mice at baseline, followi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000182425.49768.8a
更新日期:2005-09-16 00:00:00
abstract:RATIONALE:Slow nonuniform electric propagation in the border zone (BZ) of a healed myocardial infarct (MI) can give rise to reentrant arrhythmia. The extent to which this is influenced by structural rather than cellular electric remodeling is unclear. OBJECTIVE:To determine whether structural remodeling alone in the i...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.260943
更新日期:2012-07-20 00:00:00
abstract::Cellular Ca2+ regulation is abnormal in diseased hearts. We designed this study to assess the role of the Na(+)-Ca2+ exchanger in excitation-contraction coupling in surviving myocardium of the infarcted heart. We measured cellular contractions and whole-cell currents in single left ventricular myocytes isolated from t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.6.1083
更新日期:1997-12-01 00:00:00
abstract:RATIONALE:Cardiac myocyte-specific deletion of either glycogen synthase kinase (GSK)-3α and GSK-3β leads to cardiac protection after myocardial infarction, suggesting that deletion of both isoforms may provide synergistic protection. This is an important consideration because of the fact that all GSK-3-targeted drugs, ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.308544
更新日期:2016-04-15 00:00:00