Abstract:
:Local alterations in the hemodynamic environment regulate endothelial cell function, but the signal-transduction mechanisms involved in this process remain unclear. Because mitogen-activated protein (MAP) kinases have been shown to be activated by physical forces, we measured the phosphorylation and enzyme activity of MAP kinase to identify the signal events involved in the endothelial cell response to fluid shear stress. Flow at physiological shear stress (3.5 to 117 dynes/cm2) activated 42-kD and 44-kD MAP kinases present in cultured bovine aortic endothelial cells, with maximal effect at 12 dynes/cm2. Activation of a G protein was necessary, as demonstrated by complete inhibition by the nonhydrolyzable GDP analog GDP-beta S. Activation of protein kinase C (PKC) was required, as shown by inhibiting PKC with staurosporine or downregulating PKC with phorbol 12,13-dibutyrate. Both Ca(2+)-dependent and -independent PKC activity, measured by translocation and substrate phosphorylation, increased in response to flow. However, MAP kinase activation was not dependent on Ca2+ mobilization, since Ca2+ chelation had no inhibitory effect. On the basis of these findings, it is proposed that flow activates two signal-transduction pathways in endothelial cells. One pathway is Ca2+ dependent and involves activation of phospholipase C and increases in intracellular Ca2+. A new pathway, described in the present study, is Ca2+ independent and involves a G protein and increases in PKC and MAP kinase activity.
journal_name
Circ Resjournal_title
Circulation researchauthors
Tseng H,Peterson TE,Berk BCdoi
10.1161/01.res.77.5.869subject
Has Abstractpub_date
1995-11-01 00:00:00pages
869-78issue
5eissn
0009-7330issn
1524-4571journal_volume
77pub_type
杂志文章abstract::Studies were carried out to determine the contribution of cardiopulmonary receptors to the renal responses to head-out water immersion in the nonhuman primate. Immersion to the suprasternal notch was associated with significant increases in central venous pressure, urine flow, and sodium excretion. The increased sodiu...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.42.2.263
更新日期:1978-02-01 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
abstract::Increasing attention is currently devoted to the multiple roles that pericytes (also defined as mural, Rouget, or perivascular cells) may play during angiogenesis, vascular homeostasis, and pathology. Many recent excellent reviews thoroughly address these topics (see below); hence, we will not discuss them in detail h...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300203
更新日期:2013-07-19 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::To test the ability of regenerated endothelium to evoke endothelium-dependent relaxations, male Yorkshire pigs underwent balloon endothelial denudation of the proximal left anterior descending coronary artery. Endothelium-dependent responses were examined in vitro, in rings of coronary segments taken from the denuded ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.2.256
更新日期:1987-08-01 00:00:00
abstract::Cells with endothelial phenotype generated from adult peripheral blood have emerging diagnostic and therapeutic potential. This study examined the lineage relationship between, and angiogenic function of, early endothelial progenitor cells (EPCs) and late outgrowth endothelial cells (OECs) in culture. Culture conditio...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000105569.77539.21
更新日期:2003-11-28 00:00:00
abstract::A distal transcriptional enhancer has been previously reported upstream of the mouse renin gene. A homologous sequence is also present upstream of the human renin gene, but the mouse and human renin enhancers differ markedly in their ability to activate transcription of a renin promoter. Although the 2 enhancers share...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.6.479
更新日期:1999-09-17 00:00:00
abstract::Endothelial cells release several compounds, including prostacyclin, NO, and endothelium-derived hyperpolarizing factor (EDHF), that mediate the vascular effects of vasoactive hormones. The identity of EDHF remains unknown. Since arachidonic acid causes endothelium-dependent relaxations of coronary arteries through it...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.3.415
更新日期:1996-03-01 00:00:00
abstract::The direct-current magnetocardiogram, which shows the T-Q (baseline) shift, is used to clarify the cause of S-T depression induced by stress testing in the human heart. Measurements are made of the amount of baseline shift associated with the S-T depression. Results are presented of a well-documented patient, with typ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.53.2.274
更新日期:1983-08-01 00:00:00
abstract::The present study investigated the effect of adrenomedullin, a novel vasorelaxant peptide, on the migration of cultured rat vascular smooth muscle cells (SMCs) by using the Boyden-chamber method. Fetal calf serum (FCS) and platelet-derived growth factor (PDGF)-BB strongly stimulated SMC migration. Adrenomedullin clear...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.77.4.660
更新日期:1995-10-01 00:00:00
abstract::H11 kinase/Hsp22 (H11K) is a chaperone promoting cardiac cell growth and survival through the activation of Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K). In this study, we tested whether H11K-induced activation of the PI3K/Akt pathway is mediated by the bone morphogenetic protein (BMP) signaling,...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.192328
更新日期:2009-04-10 00:00:00
abstract:RATIONALE:Kawasaki disease (KD), an acute febrile vasculitis, is the most common cause of acquired heart disease in childhood; however, diagnosing KD can be difficult. OBJECTIVE:To identify unique proteomic biomarkers that can be used to facilitate earlier diagnosis of KD. METHODS AND RESULTS:We enrolled 214 children...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.305834
更新日期:2015-02-27 00:00:00
abstract:RATIONALE:Histone deacetylase (HDAC)7 is expressed in the early stages of embryonic development and may play a role in endothelial function. OBJECTIVE:This study aimed to investigate the role of HDAC7 in endothelial cell (EC) proliferation and growth and the underlying mechanism. METHODS AND RESULTS:Overexpression of...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.213165
更新日期:2010-04-16 00:00:00
abstract::Vascular endothelial cells respond to laminar shear stress by aligning in the direction of flow, a process which may contribute to atheroprotection. Here we report that localized alpha4 integrin phosphorylation is a mechanism for establishing the directionality of shear stress-induced alignment in microvascular endoth...
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
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::The present study was designed to test the ability of regenerated endothelium to evoke endothelium-dependent hyperpolarizations. Hyperpolarizations induced by serotonin and bradykinin were compared in isolated porcine coronary arteries with native or regenerated endothelium, 4 weeks after balloon endothelial denudatio...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.4.371
更新日期:1999-03-05 00:00:00
abstract::The aim was to identify energy-consuming processes, other than contraction, downregulated during moderate hypoxia ( approximately 5 micromol/L, 0.5% O(2)) and severe hypoxia (<0.5 micromol/L, <0.05% O(2)) in isolated neonatal cardiomyocytes. The metabolic response of cardiomyocytes to moderate and severe hypoxia was a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000015592.95986.03
更新日期:2002-04-19 00:00:00
abstract::Activation of protein kinase C has been implicated in the regulation of a variety of cellular reactions. Although we, and others, have found protein kinase C and its substrate proteins to be present in both membrane and cytosolic fractions in the heart, the physiologic role of this kinase in the regulation of cardiac ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.3.372
更新日期:1987-09-01 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:Plakophilin-2 (PKP2) is an essential component of the cardiac desmosome. Recent data show that it interacts with other molecules of the intercalated disc. Separate studies show preferential localization of the voltage-gated sodium channel (Na(V)1.5) to this region. OBJECTIVE:To establish the association of P...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.201418
更新日期:2009-09-11 00:00:00
abstract::We previously reported that hyperhomocysteinemia (HHcy), an independent risk factor of coronary artery disease (CAD), is associated with increased atherosclerosis and decreased plasma high-density lipoprotein cholesterol (HDL-C) in cystathionine beta-synthase-/apolipoprotein E-deficient (CBS(-/-)/apoE(-/-)) mice. We o...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000242559.42077.22
更新日期:2006-09-15 00:00:00
abstract::We have used an immunological approach to investigate the role of myosin light chain phosphorylation (MLC-Pi) in the control of contractility in smooth muscle. Our aim was to specifically inhibit myosin light chain kinase (MLCK) in the presence of physiologically activating levels of Ca2+ so that other putative Ca2(+)...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.2.457
更新日期:1991-02-01 00:00:00
abstract::The kinetics of contractions and Ca(2+) transients are slowed in myocytes from failing hearts. The mechanisms accounting for these abnormalities remain unclear. Myocardial infarction (MI) was produced by ligation of the circumflex artery in rabbits. We used confocal microscopy to record spatially resolved Ca(2+) trans...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.11.1040
更新日期:2000-11-24 00:00:00
abstract::Of 145 patients with borderline hypertension, 30% had increased resting cardiac index (QI), whereas the remainder had normal values. The specific aim of this study was to investigate cardiac regulation in patients who had normal resting QI. Eighty-five control subjects were used for comparison. At rest, patients with ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.6.199
更新日期:1975-06-01 00:00:00
abstract::This study was designed to determine if opioids were detectable in cerebrospinal fluid (CSF) and if these concentrations were altered by hemorrhagic hypotension. This study was further designed to determine the effects of topically administered opioids on pial arteriolar diameter during normotension and hypotension. C...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.4.922
更新日期:1991-04-01 00:00:00
abstract::Endocardial endothelium and endothelium of coronary vessels produce NO. Histochemical methods have suggested that coronary arterial endothelial cells contain more endothelial constitutive NO synthase (ecNOS) than does coronary venous endothelium. We have further investigated the distribution of ecNOS in cardiac endoth...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.82.2.195
更新日期:1998-02-09 00:00:00
abstract::Multiple voltage-gated K+ channels contribute to the repolarization phases of the cardiac action potential and are targets of several antiarrhythmic drugs. The Kv1.5 K+ channel gene is expressed in the heart, and heterologous expression of this gene generates a slowly inactivating K+ current. Previously, we found that...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.6.1006
更新日期:1994-12-01 00:00:00
abstract:RATIONALE:Loss-of-function studies in cardiac myocytes (CMs) are currently limited by the need for appropriate conditional knockout alleles. The factors that regulate CM maturation are poorly understood. Previous studies on CM maturation have been confounded by heart dysfunction caused by whole organ gene inactivation....
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.310283
更新日期:2017-06-09 00:00:00
abstract:RATIONALE:The high morbidity/mortality of atherosclerosis is typically precipitated by plaque rupture and consequent thrombosis. However, research on underlying mechanisms and therapeutic approaches is limited by the lack of animal models that reproduce plaque instability observed in humans. OBJECTIVE:Development and ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.113.301562
更新日期:2013-07-19 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