Abstract:
:Recent studies have demonstrated that vascular smooth muscle cells are responsive to changes in their local hemodynamic environment. The effects of shear stress on the expression of human protease activated receptor-1 (PAR-1) and tissue plasminogen activator (tPA) mRNA and protein were investigated in human aortic smooth muscle cells (HASMCs). Under conditions of low shear stress (5 dyn/cm2), PAR-1 mRNA expression was increased transiently at 2 hours compared with stationary control values, whereas at high shear stress (25 dyn/cm2), mRNA expression was decreased (to 29% of stationary control; P<0.05) at all examined time points (2 to 24 hours). mRNA half-life studies showed that this response was not due to increased mRNA instability. tPA mRNA expression was decreased (to 10% of stationary control; P<0.05) by low shear stress after 12 hours of exposure and was increased (to 250% of stationary control; P<0.05) after 24 hours at high shear stress. The same trends in PAR-1 mRNA levels were observed in rat smooth muscle cells, indicating that the effects of shear stress on human PAR-1 were not species-specific. Flow cytometry and ELISA techniques using rat smooth muscle cells and HASMCs, respectively, provided evidence that shear stress exerted similar effects on cell surface-associated PAR-1 and tPA protein released into the conditioned media. The decrease in PAR-1 mRNA and protein had functional consequences for HASMCs, such as inhibition of [Ca2+] mobilization in response to thrombin stimulation. These data indicate that human PAR-1 and tPA gene expression are regulated differentially by shear stress, in a pattern consistent with their putative roles in several arterial vascular pathologies.
journal_name
Circ Resjournal_title
Circulation researchauthors
Papadaki M,Ruef J,Nguyen KT,Li F,Patterson C,Eskin SG,McIntire LV,Runge MSdoi
10.1161/01.res.83.10.1027subject
Has Abstractpub_date
1998-11-16 00:00:00pages
1027-34issue
10eissn
0009-7330issn
1524-4571journal_volume
83pub_type
杂志文章abstract::Although the ultrasonic pulsatility index (PI) is used as a test of arterial inflow, the relationship between proximal arterial stenosis and PI has not been fully evaluated. In a series of experiments on dogs, over 200 measurements of pressure, flow (using an indwelling electromagnetic flowmeter), and PI were made dis...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.46.4.470
更新日期:1980-04-01 00:00:00
abstract::We studied the specificity of uptake of infarct-imaging agents for reversibly or irreversibly injured myocardium independently of blood flow by using intact beating fetal mouse hearts in organ culture. Reversible injury resulted from deprivation of oxygen and glucose for 4 hours at 37 degrees C; irreversible injury, f...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.6.860
更新日期:1976-12-01 00:00:00
abstract:RATIONALE:Proteasomal degradation is altered in many disease phenotypes including cardiac hypertrophy, a prevalent condition leading to heart failure. Our recent investigations identified heterogeneous subpopulations of proteasome complexes in the heart and implicated multiple mechanisms for their regulation. OBJECTIV...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.222364
更新日期:2010-10-29 00:00:00
abstract::The mechanism of adenosine-induced inhibition of Ca2+ currents was studied by recording single-channel Ca2+ currents from cell-attached patches on isolated guinea pig ventricular cells with pipettes containing 50 or 100 mM Ba2+. Numerous 100-msec depolarization steps were applied repetitively at 2 Hz from the resting ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.5.1134
更新日期:1990-11-01 00:00:00
abstract::Proteases of the plasminogen activator (PA) and matrix metalloproteinase (MMP) system play an important role in smooth muscle cell (SMC) migration and neointima formation after vascular injury. Inhibition of either PAs or MMPs has previously been shown to result in decreased neointima formation in vivo. To inhibit bot...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000041418.51906.57
更新日期:2002-11-15 00:00:00
abstract::Hyperhomocysteinemia, a risk factor for cardiovascular disease, is caused by nutritional or genetic disturbances in homocysteine metabolism. A polymorphism in methylenetetrahydrofolate reductase (MTHFR) is the most common genetic cause of mild hyperhomocysteinemia. To examine mechanisms by which an elevation in plasma...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000204825.66410.0b
更新日期:2006-03-03 00:00:00
abstract:RATIONALE:Molecular imaging is useful for longitudinal assessment of engraftment. However, it is not known which factors, other than cell number, can influence the molecular imaging signal obtained from reporter genes. OBJECTIVE:The effects of cell dissociation/suspension on cellular bioenergetics and the signal obtai...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.273375
更新日期:2013-02-01 00:00:00
abstract::The purpose of this study was to investigate if myogenic responses of isolated coronary arterioles were dependent on an intact, functional endothelium. Arterioles were located in situ by intracoronary perfusion with india ink-gelatin solution and then dissected and cannulated at both ends with glass micropipettes. Int...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.3.860
更新日期:1990-03-01 00:00:00
abstract::The consequences of endothelin receptor activation were examined in atrial tumor myocytes derived from transgenic mice (AT-1 cells). Endothelin-1 (endothelin) stimulates phosphoinositide hydrolysis in a dose-dependent manner. Endothelin also induces the rapid and transient translocation of protein kinase C (PKC)-epsil...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.4.724
更新日期:1996-04-01 00:00:00
abstract::The role of Ca(2+)-dependent potassium channels in mediating vascular responses to activation of adenylate cyclase in vivo is not known. The goal of this study was to examine the hypothesis that dilatation of cerebral arterioles in response to activation of adenylate cyclase is mediated by activation of Ca(2+)-depende...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.6.1057
更新日期:1995-06-01 00:00:00
abstract::Vascular endothelial growth factors (VEGFs) and their receptors have emerged as central regulators of the angiogenic process. However, involvement of VEGF-B, one of these factors, in angiogenesis remains obscure. Mice received subcutaneous injection of Matrigel alone or Matrigel with human recombinant protein rhVEGF-B...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000081594.21764.44
更新日期:2003-07-25 00:00:00
abstract::Endothelins exert potent excitatory cardiac effects by acting on specific receptors on myocytes. In this study, we have examined the signal transduction mechanism for the chronotropic effect of endothelins in guinea pig atria. A competition binding of [125I]endothelin 1 ([125I]ET-1) using the recently developed ETA re...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.2.284
更新日期:1995-02-01 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: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::Patients with peripheral artery disease (PAD) are at heightened risk of both systemic cardiovascular adverse events, as well as limb-related morbidity. The optimal management of patients with PAD requires a comprehensive treatment strategy incorporating both lifestyle changes, including smoking cessation and exercise,...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.114.303505
更新日期:2015-04-24 00:00:00
abstract::Bone morphogenetic peptides (BMPs), a family of cytokines critical to normal development, were recently implicated in the pathogenesis of familial pulmonary arterial hypertension. The type-II receptor (BMPRII) is required for recognition of all BMPs, and targeted deletion of BMPRII in mice results in fetal lethality b...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000126047.82846.20
更新日期:2004-04-30 00:00:00
abstract::To see how serotonin affects filtration from lung vessels, we measured vascular pressures, lung lymph flow, lung lymph and blood plasma protein concentrations, arterial blood gases, cardiac output, and lung water content in unanesthetized sheep before and during intravenous serotonin infusions and compared serotonin e...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.6.761
更新日期:1975-06-01 00:00:00
abstract::To determine whether the vasoconstriction evoked by A1-adenosine receptor stimulation in the skin circulation caused the release of other substances or whether A1 stimulation modulated the vasoconstriction evoked by other compounds, a potent A1-selective, synthetic agonist, cyclohexyladenosine (CHA), was topically app...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.3.683
更新日期:1991-03-01 00:00:00
abstract::Although it has been established that myocyte enhancer factor 2 (MEF2) plays pivotal roles in the development of the cardiovascular system as well as skeletal muscle cells, little is known of its role in vascular inflammatory diseases such as atherosclerosis and restenosis after angioplasty. To investigate the role of...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000134631.75684.4A
更新日期:2004-07-09 00:00:00
abstract::Transmural heterogeneity of myocardial metabolism and function are present in the left ventricle under normal and ischemic conditions. To determine if endocardial versus epicardial differences of [Ca2+]i are also present, perfused rat heart studies using indo-1 fluorescence as an index of [Ca2+]i were performed in the...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.5.1082
更新日期:1993-05-01 00:00:00
abstract::The major goal of this study was to determine the interactions of VLDL surface and core lipids with the artery wall. We first demonstrated in vitro that surface lipid in VLDL could be traced using the phospholipid-like fluorescent probe 1,1'-dioctadecyl-3,3, 3',3'-tetramethyl-indocarbocyanine (DiI). The core of VLDL p...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.7.768
更新日期:2000-04-14 00:00:00
abstract::Whole-cell voltage-clamp experiments were performed on enzymatically dissociated single ventricular myocytes harvested from feline endocardial and epicardial surfaces. The studies were designed to test the hypothesis that the differences in the amplitude of transient outward current (Ito) contribute to the difference ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.5.1287
更新日期:1990-11-01 00:00:00
abstract::Lipid rafts are discrete membrane subdomains rich in sphingolipids and cholesterol. In ventricular myocytes a function of caveolae, a type of lipid rafts, is to concentrate in close proximity several proteins of the beta-adrenergic transduction pathway. We have investigated the subcellular localization of HCN4 channel...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000127621.54132.AE
更新日期:2004-05-28 00:00:00
abstract:RATIONALE:Congenital heart disease (CHD) is among the most common birth defects. Most cases are of unknown pathogenesis. OBJECTIVE:To determine the contribution of de novo copy number variants (CNVs) in the pathogenesis of sporadic CHD. METHODS AND RESULTS:We studied 538 CHD trios using genome-wide dense single nucle...
journal_title:Circulation research
pub_type: 临床试验,杂志文章
doi:10.1161/CIRCRESAHA.115.304458
更新日期:2014-10-24 00:00:00
abstract::Many members of the two-pore-domain potassium (K(+)) channel family have been detected in the mammalian heart but the endogenous correlates of these channels still have to be identified. We investigated whether I(KAA), a background K(+) current activated by negative pressure (stretch) and by arachidonic acid (AA) and ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1601.094979
更新日期:2001-08-17 00:00:00
abstract::The responses of cardiac mitochondria to anoxia may be evaluated in terms of the oxidation-reduction state of the electron carriers and the ability of the mitochondria to function in energy-linked reactions. The previous detailed evaluation of the oxygen requirements for electron transfer in mitochondria is here exten...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1976-05-01 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:RATIONALE:The heart contains abundant interstitial and perivascular fibroblasts. Traditional views suggest that, under conditions of mechanical stress, cytokines, growth factors, and neurohumoral mediators stimulate fibroblast activation, inducing ECM (extracellular matrix) protein synthesis and promoting fibrosis and ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.314438
更新日期:2019-04-12 00:00:00
abstract::Angiotensin-converting enzyme inhibitor was used in dogs with uranyl nitrate-induced acute renal failure to evaluate (1) a possible protective effect of angiotensin blockade and (2)the role of angiotensin II in the generation of renal failure in this model. Angiotensin-converting enzyme inhibitor treatment attenuated ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.51.2.216
更新日期:1982-08-01 00:00:00
abstract::There is now overwhelming evidence to support lowering LDL-c (low-density lipoprotein cholesterol) to reduce cardiovascular morbidity and mortality. Statins are a class of drugs frequently prescribed to lower cholesterol. However, in spite of their wide-spread use, discontinuation and nonadherence remains a major gap ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.118.312782
更新日期:2019-01-18 00:00:00