Abstract:
:Blockade of angiotensin type 1 (AT1) receptors induces smooth muscle cell (SMC) death and regression of aortic hypertrophy in spontaneously hypertensive rats (SHR). We postulated that SMC death and vascular remodeling in this model may be attenuated by z-Val-Ala-Asp(OMe)-CH2F (z-VAD-fmk), a tripeptide inhibitor of caspase enzymes mediating apoptosis. To determine the time course of SMC death and aortic remodeling, SHR were treated with losartan (30 mg/kg per day) for up to 9.5 days. Transient SMC apoptosis occurred in the aortic media with a peak around day 5 of treatment, with increases in the Bax to Bcl-2 protein ratio (>3-fold), in active caspase-3 (5.6-fold), in TUNEL-positive nuclei (19-fold), preceding by 24 hours the peak activation of capase-9 (3.8-fold), and significant reductions in SMC number (46%) and aortic cross-sectional area (8.5%) at 5.5 days. The decrease in total aortic DNA reached significance at 6.5 days (29%). Blood pressure reduction with losartan was progressive and reached significance at day 7 of treatment. Next, we examined the causal link between vascular apoptosis and remodeling. SHR received placebo or losartan (30 mg/kg per day) for 6 days. During the last 24 hours, a subgroup of losartan-treated rats received 3 IV injections of z-VAD-fmk (cumulative dose: 4.4 mg x kg(-1)). All other rats received the vehicle, DMSO. The 24-hour cotreatment with z-VAD-fmk effectively prevented losartan-induced caspase-3 activation and internucleosomal DNA fragmentation, as well as SMC depletion and the reductions in aortic mass and DNA content. Together, these data suggest that caspase-dependent SMC death mediates the early phase of vascular remodeling in response to AT1 receptor blockade in this model of hypertension.
journal_name
Circ Resjournal_title
Circulation researchauthors
Marchand EL,Der Sarkissian S,Hamet P,deBlois Ddoi
10.1161/01.RES.0000065619.36118.20subject
Has Abstractpub_date
2003-04-18 00:00:00pages
777-84issue
7eissn
0009-7330issn
1524-4571pii
01.RES.0000065619.36118.20journal_volume
92pub_type
杂志文章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::We previously have shown that alpha-adrenergic stimulation of canine Purkinje fibers and rat ventricle decreases automaticity. Experiments on rat ventricular myocytes in tissue culture have suggested that the decrease in automaticity induced by alpha-adrenergic stimulation depends on the development of sympathetic inn...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.2.315
更新日期:1988-02-01 00:00:00
abstract:RATIONALE:Cell therapy is a promising option for the treatment of acute or chronic myocardial ischemia. The intracoronary infusion of cells imposes the potential risk of cell clotting, which may be prevented by the addition of anticoagulants. However, a comprehensive analysis of the effects of anticoagulants on the fun...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.265678
更新日期:2012-09-14 00:00:00
abstract::The regeneration of new myocardium by stem or progenitor cells is an important therapeutic option. Cellular or nuclear fusion is considered as an alternative to cell reprogramming by transdifferentiation. However, the generation of hybrid cells may also be a consequence of a transient transmembrane exchange of protein...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000168650.23479.0c
更新日期:2005-05-27 00:00:00
abstract::To determine if intestinal microvascular growth is impaired in diabetic juvenile animals, a segment of the terminal ileum was marked and the microvasculature of this segment observed at the age of 5 weeks and again at the age of 10-11 weeks in normal and diabetic Sprague Dawley rats. Diabetes was induced by streptozot...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.2.429
更新日期:1988-08-01 00:00:00
abstract::Fluid shear stress caused by blood flow is a major determinant of vascular remodeling and arterial tone and can lead to development of atherosclerosis. The endothelial monolayer in vivo acts as a signal transduction interface for hemodynamic forces; these forces determine the shape, cytoskeletal organization, and func...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000200162.94463.d7
更新日期:2006-02-03 00:00:00
abstract::Nuclear factor kappa B (NF-kappaB) participates in hypertension-induced vascular and target-organ damage. We tested whether or not endothelial cell-specific NF-kappaB suppression would be ameliorative. We generated Cre/lox transgenic mice with endothelial cell-restricted NF-kappaB super-repressor IkappaBalphaDeltaN (T...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.150474
更新日期:2007-08-03 00:00:00
abstract::The effect of sulfinpyrazone on endothelial injury induced by homocysteine has been studied both in vitro, using cultured human umbilical vein endothelial cells, and in vivo, using a primate model of homocysteine-induced arteriosclerosis. Oral sulfinpyrazone (250 mumol/kg body weight per day in three divided doses) in...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.53.6.731
更新日期:1983-12-01 00:00:00
abstract::Pathological remodeling of the left ventricle (LV) after myocardial infarction (MI) is a major cause of heart failure. Although cardiac hypertrophy after increased loading conditions has been recognized as a clinical risk factor for human heart failure, it is unknown whether post-MI hypertrophic remodeling of the myoc...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000118597.54416.00
更新日期:2004-02-20 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::The ionic currents that cross the myocardial membrane during cardiac activation have a corresponding return path in the extracellular space. The transmembrane current (Im) during activation of cardiac cells in situ has previously been envisioned only in mathematical models. We have developed a remarkably simple in viv...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.2.424
更新日期:1993-02-01 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:RATIONALE:Myofibroblasts are believed to evolve from precursor cells; however, whether noncardiomyocyte cardiac cells (NMCCs; ie, endothelial cells, smooth muscle cells, pericytes, and fibroblasts) that have been derived from human-induced pluripotent stem cells (hiPSCs) can transdifferentiate into myofibroblast-like c...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.313094
更新日期:2018-12-07 00:00:00
abstract::The extracellular and intracellular potassium (K+) activities of isolated superfused rabbit atrial muscle were measured using K+-sensitive liquid ion exchanger microelectrodes. When the pH of the bathing medium was decreased from 7.5 to 6.8, intracellular K+ activity fell and extracellular K+ activity rose from a mean...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.5.678
更新日期:1976-11-01 00:00:00
abstract::Some statistical techniques for analyzing the kinds of studies typically reported in Circulation Research are described. Particular emphasis is given to the comparison of means from more than two populations, the joint effect of several experimentally controlled variables, and the analysis of studies with repeated mea...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.47.1.1
更新日期:1980-07-01 00:00:00
abstract:RATIONALE:Our insights into physiological and pathophysiological cardiac excitation-contraction coupling has greatly benefited from significant advancement in optical technologies such as high-speed confocal microscopy. This has pushed pixel dwell times into the time domain of nanoseconds, resulting in low signal-to-no...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.266403
更新日期:2012-06-22 00:00:00
abstract::Endothelial cells, either in vivo or freshly isolated, respond when exposed to muscarinic agonists with an increase in cytosolic free calcium concentration ([Ca2+]i) and release of endothelium-derived relaxing factor (EDRF). When placed in culture, however, endothelial cells rapidly lose these responses, which may be ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.2.234
更新日期:1992-02-01 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::In intact porcine aorta, endothelium-derived nitric oxide released on thrombin stimulation inhibits the concomitant production of endothelin. Experiments were designed to examine the effect of hirudin (which inactivates thrombin) and the nitrovasodilators nitroglycerin and 3-morpholinosydnonimine on the spontaneous an...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.6.1768
更新日期:1991-06-01 00:00:00
abstract::An extensive investigation of the cardiac actions of phorbol esters and the potential role of the Na(+)-H+ exchanger in those actions was carried out using isolated rat hearts. Sixty minutes of perfusion with 10(-9) M phorbol 12-myristate 13-acetate (PMA) or 10(-8) M phorbol 12,13-dibutyrate (PDBu) produced marked car...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.4.1114
更新日期:1991-10-01 00:00:00
abstract::It has been demonstrated by other investigators that endothelium-dependent vasodilators are more effective on arterial tissue than on venous tissue. The purpose of this study was to determine if this was due to a difference in the sensitivity of arterial and venous smooth muscle to the endothelial dilator (EDRF) or to...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.60.4.626
更新日期:1987-04-01 00:00:00
abstract::Caspase-1 processes the interleukin (IL)-1beta and IL-18 inactive precursors to the biologically active cytokines that are known to have proatherogenic effects. The present study investigated the genetic variability of the CASP1 gene and plasma levels of caspase-1 in relation to cardiovascular risk. In Europeans, 3 ta...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000232324.87983.4b
更新日期:2006-07-07 00:00:00
abstract::Life threatening ventricular arrhythmias leading to sudden cardiac death are a major cause of morbidity and mortality. In the absence of structural heart disease, these arrhythmias, especially in the younger population, are often an outcome of genetic defects in specialized membrane proteins called ion channels. In th...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.118.311209
更新日期:2018-07-06 00:00:00
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::Isolated cardiac conduction disease is an autosomal dominant defect that includes various combinations of bundle branch or fascicular blocks. These defects can cause sudden death due to a complete heart block. We used a genome-wide screening approach with polymorphic (CA)n repeat markers to determine the chromosomal p...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.77.4.735
更新日期:1995-10-01 00:00:00
abstract::Reperfusion of globally ischemic rat hearts causes the generation of inositol(1,4,5)trisphosphate [Ins(1,4,5)P3] and the initiation of arrhythmias. These responses are mediated by alpha1-adrenergic receptors (ARs), but the subtype of receptor involved has not been identified. Under normoxic conditions, hearts from tra...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.12.1232
更新日期:1998-12-14 00:00:00
abstract:RATIONALE:Disruption of endothelial barrier function and neutrophil-mediated injury are two major mechanisms underlying the pathophysiology of sepsis-induced acute lung injury (ALI). Recently we reported that endotoxin induced activation of RhoA in mice lungs that led to the disruption of endothelial barrier and lung e...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.195883
更新日期:2009-09-11 00:00:00
abstract::The rate of renin secretion from renal juxtaglomerular (JG) cells is the major determinant of the activity of the renin-angiotensin system. However, the mechanisms involved in the excretion and turnover of secretory granules in the JG cells remain obscure. Therefore, in the present study, the whole-cell patch-clamp te...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.8.929
更新日期:1999-04-30 00:00:00
abstract::We developed a mouse myocardial preparation to study cellular dysfunction in acute coxsackievirus myocarditis. Thin right ventricular papillary muscles from normal mice (n = 8) were compared with muscles from mice 7 days after coxsackievirus infection (n = 7). Sarcomere shortening was studied with laser diffraction (H...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.3.462
更新日期:1994-09-01 00:00:00
abstract::The purpose of this study was to determine whether biphasic restitution of action potential duration (APD) in ventricular muscle permits the development of complex dynamic behavior. Such behavior is expected because of the steep ascending slope of restitution and the presence of a maximum. Action potentials recorded f...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.5.915
更新日期:1995-05-01 00:00:00