Abstract:
:The vasoactive mechanisms of the serine protease alpha-thrombin were examined in isolated coronary arteries from dogs. In resting coronary arteries with endothelium, alpha-thrombin caused concentration-dependent contractions that were characterized by an initial transient relaxation followed by slowly developing sustained contractions. The vascular actions of alpha-thrombin were mimicked by the thrombin receptor-activating peptide (TRAP) SFLLRNP, a synthetic peptide based on the cleaved terminus of the thrombin receptor domain. Treatment of the arteries with N omega-nitro-L-arginine or removal of endothelium abolished the transient relaxations and enhanced the contractions, indicating that the transient relaxations were mediated by the concurrent release of endothelium-derived nitric oxide. alpha-Thrombin that had been catalytically inactivated with the irreversible inhibitor by use of D-Phe-Pro-Arg-chloromethyl ketone did not cause contractions, indicating the requirement of proteolytic cleavage by alpha-thrombin to induce contractions. In contrast to TRAP, alpha-thrombin-induced contractions were blocked by hirudin (a specific thrombin inhibitor), nifedipine and diltiazem (Ca2+ channel blockers), or staurosporine and calphostin C (protein kinase C inhibitors). Unlike alpha-thrombin, which undergoes homologous desensitization, TRAP failed to cause desensitization to subsequent stimulation by alpha-thrombin or TRAP. These observations support the hypothesis that vasoactive actions of alpha-thrombin are mediated by a mechanism that involves cleavage at the active site to expose a new NH2 terminus that activates the thrombin receptor. Further, the dissociation between alpha-thrombin and the synthetic receptor peptide in signal transduction and dissimilar desensitizing properties suggest the existence of distinct thrombin receptor subtypes and/or signaling events in vascular smooth muscle.
journal_name
Circ Resjournal_title
Circulation researchauthors
Tesfamariam Bdoi
10.1161/01.res.74.5.930subject
Has Abstractpub_date
1994-05-01 00:00:00pages
930-6issue
5eissn
0009-7330issn
1524-4571journal_volume
74pub_type
杂志文章abstract::Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses fo...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300269
更新日期:2013-08-30 00:00:00
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journal_title:Circulation research
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doi:10.1161/01.res.83.11.1165
更新日期:1998-11-30 00:00:00
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doi:10.1161/CIRCRESAHA.111.258871
更新日期:2012-02-03 00:00:00
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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:RATIONALE:Individuals with naturally occurring loss-of-function proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations experience reduced low-density lipoprotein cholesterol levels and protection against cardiovascular disease. OBJECTIVE:The goal of this study was to assess whether genome editing using a clus...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.304351
更新日期:2014-08-15 00:00:00
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pub_type: 杂志文章
doi:10.1161/hh0402.105096
更新日期:2002-03-08 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.57.6.864
更新日期:1985-12-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.3.600
更新日期:1989-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.70.2.438
更新日期:1992-02-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.4.1027
更新日期:1990-10-01 00:00:00
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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::Pinacidil belongs to a novel group of compounds that enhance the potassium permeability of vascular smooth muscle. Evidence also exists that this drug enhances the potassium permeability of cardiac tissue. The purpose of the present investigation was to determine if pinacidil alters potassium-channel activity in heart...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.2.436
更新日期:1989-08-01 00:00:00
abstract::MicroRNAs act as negative regulators of gene expression by inhibiting the translation or promoting the degradation of target mRNAs. Because individual microRNAs often regulate the expression of multiple target genes with related functions, modulating the expression of a single microRNA can, in principle, influence an ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.108.183426
更新日期:2008-10-24 00:00:00
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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
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000086942.13523.88
更新日期:2003-08-08 00:00:00
abstract::Alveolar epithelial beta-adrenergic receptor (betaAR) activation accelerates active Na+ transport in lung epithelial cells in vitro and speeds alveolar edema resolution in human lung tissue and normal and injured animal lungs. Whether these receptors are essential for alveolar fluid clearance (AFC) or if other mechani...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000125623.56442.20
更新日期:2004-04-30 00:00:00
abstract::In adult mammals, massive sudden loss of cardiomyocytes after infarction overwhelms the limited regenerative capacity of the myocardium, resulting in the formation of a collagen-based scar. Necrotic cells release danger signals, activating innate immune pathways and triggering an intense inflammatory response. Stimula...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.303577
更新日期:2016-06-24 00:00:00
abstract::Autoregulatory responses to alterations in arterial or venous perfusion pressure were determined for individual arterioles within the rat cremaster muscle. The cremaster muscle of pentobarbital anesthetized rats (50 mg/kg, ip) was surgically exposed and maintained in a controlled tissue bath for visualization by in vi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.51.1.43
更新日期:1982-07-01 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::Smooth muscle cell migration in response to platelet-derived growth factor (PDGF) is a key event in several vascular pathologies, including atherosclerosis and restenosis. PDGF increases intracellular levels of reactive oxygen species (ROS) in vascular smooth muscle cells (VSMCs), but the ROS sensitivity of migration ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000126848.54740.4A
更新日期:2004-05-14 00:00:00
abstract::Reactive oxygen species and reactive nitrogen species are biological molecules that play important roles in cardiovascular physiology and contribute to disease initiation, progression, and severity. Because of their ephemeral nature and rapid reactivity, these species are difficult to measure directly with high accura...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/RES.0000000000000110
更新日期:2016-08-19 00:00:00
abstract::The relations between atrial natriuretic peptide (ANP) binding sites in the renal medulla, plasma ANP concentration, and ventricular dysfunction have been studied in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. Plasma ANP concentration was measured by radioimmunoassay, and quantit...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.1.155
更新日期:1988-01-01 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::Mechanical forces participate in morphogenesis from the level of individual cells to whole organism patterning. This article reviews recent research that has identified specific roles for mechanical forces in important developmental events. One well defined example is that dynein-driven cilia create fluid flow that de...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.108.175331
更新日期:2008-08-01 00:00:00
abstract:RATIONALE:The mutation A341V in the S6 transmembrane segment of KCNQ1, the α-subunit of the slowly activating delayed-rectifier K(+) (I(Ks)) channel, predisposes to a severe long-QT1 syndrome with sympathetic-triggered ventricular tachyarrhythmias and sudden cardiac death. OBJECTIVE:Several genetic risk modifiers have...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.249482
更新日期:2012-01-20 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::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 smo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.10.1027
更新日期:1998-11-16 00:00:00
abstract::Calcium uptake was measured in homogenates and microsomal preparations enriched in sarcoplasmic reticulum vesicles isolated from hearts of hypertrophic (BIO 14.6) and dilated (BIO 53.58) cardiomyopathic as well as control (F1B) Syrian hamsters at 3, 7, 9, and 11 months of age. Calcium uptake studies were done using th...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.1.81
更新日期:1988-01-01 00:00:00
abstract::Platelet activation is markedly increased during coronary thrombolysis and limits the response to thrombolytic therapy. A possible mediator of platelet activation in this setting is thromboxane (TX) A2, a potent platelet agonist formed in greatly increased amounts during coronary thrombolysis in man. To address this h...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.1.83
更新日期:1989-07-01 00:00:00
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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