Abstract:
:On endothelial cells, thrombin binds to thrombomodulin (TM), an integral membrane-bound glycoprotein, and to protease-activated receptors (PARs). Thrombin binding to TM modulates endothelial cell and smooth muscle cell proliferation mediated through PAR1. We studied the phosphorylation and nuclear translocation of extracellular signal-regulated kinases (ERKs) 1 and 2 in human umbilical vein endothelial cells activated by thrombin. Thrombin and thrombin receptor-activating peptide (TRAP)-induced DNA synthesis were significantly inhibited by PD98059, an inhibitor of ERK phosphorylation. Immunoblots of phosphorylated ERKs (pERKs) and immunocytochemical studies of pERK localization revealed differences in the signal generated by thrombin and TRAP. After a short activation (15 minutes), the phosphorylation and the intracellular localization of pERKs were the same with the 2 agonists. After 4 hours, however, pERKs were visualized in the nuclei of thrombin-activated cells but barely detectable in TRAP-activated cells. Moreover, after 4 hours, the pERKs were visualized in the nuclei of cells stimulated by TRAP in the presence of a thrombin mutant that bound to TM, whereas they were around the nuclei in cells stimulated by thrombin in the presence of a monoclonal antibody preventing thrombin binding to TM. The results demonstrate that ERKs are involved in human umbilical vein endothelial cell DNA synthesis mediated by PAR agonists, that the duration of pERK nuclear retention is in inverse ratio to the mitogenic response, and that in addition to its role in the regulation of blood coagulation, TM acts as a thrombin receptor that modulates the duration of pERK nuclear retention and cell proliferation in response to thrombin.
journal_name
Circ Resjournal_title
Circulation researchauthors
Olivot JM,Estebanell E,Lafay M,Brohard B,Aiach M,Rendu Fdoi
10.1161/hh0701.088769subject
Has Abstractpub_date
2001-04-13 00:00:00pages
681-7issue
7eissn
0009-7330issn
1524-4571journal_volume
88pub_type
杂志文章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
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.4.570
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journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.309115
更新日期:2017-01-20 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.res.0000038487.19924.18
更新日期:2002-11-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.44.6.759
更新日期:1979-06-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.45.1.26
更新日期:1979-07-01 00:00:00
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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
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pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.303641
更新日期:2015-03-13 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.2.231
更新日期:1985-02-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.12.1139
更新日期:1999-12-03 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.214155
更新日期:2010-02-19 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.4.539
更新日期:1986-04-01 00:00:00
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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::In the early (3-day) stage of development, long-lasting openings of the L-type Ca2+ channels (mode 2) occur in embryonic chick heart cells. Since mode-2 behavior is infrequently observed in adult heart cells of other species, in the present study, developmental change in behavior of the Ca2+ channel was examined in yo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.2.376
更新日期:1992-08-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000033988.13062.7c
更新日期:2002-09-20 00:00:00
abstract::The effects of exercise training on the coronary vasodilation following activation of the Bezold-Jarisch reflex were examined in conscious dogs. Mongrel dogs were chronically instrumented using sterile techniques for measurements of systemic hemodynamics and left circumflex coronary blood flow (CBF). With the heart ra...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.6.868
更新日期:1997-06-01 00:00:00
abstract::A narrow zone of block in isolated false tendon preparations was created by perfusion of the central compartment (gap) of a three-compartment tissue bath with either an isotonic sucrose solution or a solution designed to mimic the extracellular milieu in ischemic tissue. Driven responses on the proximal side of the ga...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.49.5.1129
更新日期:1981-11-01 00:00:00
abstract:RATIONALE:Closure of the ductus arteriosus (DA) is essential for the transition from fetal to neonatal patterns of circulation. Initial PO2-dependent vasoconstriction causes functional DA closure within minutes. Within days a fibrogenic, proliferative mechanism causes anatomic closure. Though modulated by endothelial-d...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.300285
更新日期:2013-03-01 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::In recent year, increasing evidence suggests that noncoding RNAs play important roles in the regulation of tissue homeostasis and pathophysiological conditions. Besides small noncoding RNAs (eg, microRNAs), >200-nucleotide long transcripts, namely long noncoding RNAs (lncRNAs), can interfere with gene expressions and ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.302521
更新日期:2015-02-13 00:00:00
abstract::Ventricular/vascular coupling dynamics and regional hemodynamics of five hypertensive baboons with concentric left ventricular (LV) hypertrophy (mean arterial pressure +/- SD, 148 +/- 16 mm Hg; LV mass/body weight ratio 3.42 +/- 0.8) were compared with five normotensive controls (mean arterial pressure 89 +/- 3 mm Hg;...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.4.798
更新日期:1988-10-01 00:00:00
abstract:RATIONALE:Smooth muscle precursor cells have previously been reported to reside in bone marrow and in the circulation, but little is currently known regarding the proximate stimuli for smooth muscle cell differentiation of these putative progenitors. OBJECTIVE:Because local thrombin generation occurs as an initial res...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.199984
更新日期:2009-07-31 00:00:00
abstract::Animal and preliminary human studies of adult cell therapy following acute myocardial infarction have shown an overall improvement of cardiac function. Myocardial and vascular regeneration have been initially proposed as mechanisms of stem cell action. However, in many cases, the frequency of stem cell engraftment and...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.108.176826
更新日期:2008-11-21 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2003-12-12 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.182535
更新日期:2009-01-30 00:00:00
abstract::Choline acetyltransferase is the enzyme that catalyzes the biosynthesis of acetylcholine, the neurotransmitter of the pre- and postganglionic parasympathetic system. To assess the extent of parasympathetic innervation, enzyme activity was measured in specialized and contractile regions throughout the guinea pig heart....
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.42.5.657
更新日期:1978-05-01 00:00:00
abstract::Myocardial stunning is characterized by decreased myofilament Ca2+ responsiveness. To investigate the molecular basis of stunned myocardium, we performed PAGE and Western immunoblot analysis of the contractile proteins. Isolated rat hearts were retrogradely perfused at 37 degrees C for either 50 minutes (control group...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
abstract::Neuropeptide Y (NPY) is stored with norepinephrine in sympathetic nerves throughout the cardiovascular system and is released during activation of the sympathetic nervous system in humans and other animals. After stimulation of the cardiac sympathetic nerves in anesthetized dogs, the action of the vagus nerve on heart...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.1.193
更新日期:1990-07-01 00:00:00
abstract:RATIONALE:Flecainide, a class 1c antiarrhythmic, has emerged as an effective therapy in preventing arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) refractory to β-adrenergic receptor blockade. It has been proposed that the clinical efficacy of flecainide in CPVT is because of t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.305347
更新日期:2015-04-10 00:00:00
abstract::Congenital heart disease (CHD) is the most common congenital anomaly in newborn babies. Cardiac malformations have been produced in multiple experimental animal models, by perturbing selected molecules that function in the developmental pathways involved in myocyte specification, differentiation, or cardiac morphogene...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.112.300853
更新日期:2013-02-15 00:00:00