Abstract:
:Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis that stimulates proliferation, migration, and proteolytic activity of endothelial cells. Although the mitogenic activity of VEGF is endothelial cell specific, recent reports indicate VEGF is able to stimulate chemotaxis and tissue factor production in monocytes. VEGF-stimulated activity in monocytes is mediated by the VEGF receptor flt-1. The purpose of the present study was to investigate the effects of VEGF on another major cell type in the vascular wall, namely, the vascular smooth muscle cell (SMC). Using cultured cells, we showed that VEGF has a minimal mitogenic effect on SMCs, which is in accordance with published data. However, VEGF treatment significantly enhanced production of matrix metalloproteinase (MMP)-1, -3, and -9 by human SMCs. The upregulation of MMP-1 and MMP-9 was pronounced, and the stimulation for MMP-3 was less prominent. Stimulation could be demonstrated at both protein and mRNA levels, as reflected by ELISA, zymography, and Northern blot analysis. To explore the signal transduction pathway for the effect of VEGF on SMCs, we studied the expression of 2 high-affinity VEGF receptors, the kinase insert domain-containing receptor (KDR) and flt-1, in human SMCs. Both reverse transcriptase-polymerase chain reaction and immunoblotting revealed the expression of flt-1. Immunoprecipitation followed by immunoblotting illustrated phosphorylation of the flt-1 receptor after VEGF treatment. Similar methodology failed to detect expression of KDR in human SMCs. These data suggest the role of flt-1 in mediating VEGF-stimulated MMP expression of SMCs. The physiological relevance of MMP upregulation was studied by examining VEGF-stimulated SMC migration through 2 synthetic extracellular matrix barriers, Matrigel and Vitrogen. Our results indicate that VEGF treatment accelerated SMC migration through both barriers, and that this response was blocked by MMP inhibition in Matrigel, which supports a permissive role of MMP in SMC migration. These data are the first to show a direct effect of VEGF on SMCs. SMC-derived MMPs may be an additional source of proteases to digest vascular basement membrane, which is a crucial step in the initial stage of angiogenesis. The MMPs may also contribute to SMC migration in angiogenesis and atherogenesis.
journal_name
Circ Resjournal_title
Circulation researchauthors
Wang H,Keiser JAdoi
10.1161/01.res.83.8.832subject
Has Abstractpub_date
1998-10-19 00:00:00pages
832-40issue
8eissn
0009-7330issn
1524-4571journal_volume
83pub_type
杂志文章abstract::We recently showed that the transient expression of a hemagglutinin (HA) epitope-tagged, constitutively active mutant of the G protein alpha(q) subunit (HAalpha(q)*) in the hearts of transgenic mice is sufficient to induce cardiac hypertrophy and dilatation that continue to progress after HAalpha(q)* protein becomes u...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.11.1085
更新日期:1999-11-26 00:00:00
abstract::Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by life threatening arrhythmias and mutations in the gene encoding the ryanodine receptor (RyR2). Disagreement exists on whether (1) RyR2 mutations induce abnormal calcium transients in the absence of adrenergic stimulat...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000235869.50747.e1
更新日期:2006-08-04 00:00:00
abstract::Therapy directed against the toxic effects of reactive oxygen species may reduce the final extent of ischemic injury in otherwise viable tissue irreversibly injured by the abrupt reoxygenation of reperfusion. In four groups of dogs, superoxide dismutase plus catalase (groups I-III) or saline (controls) (group IV) was ...
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pub_type: 杂志文章
doi:10.1161/01.res.54.3.277
更新日期:1984-03-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.111.243956
更新日期:2012-06-08 00:00:00
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journal_title:Circulation research
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doi:10.1161/CIRCRESAHA.107.168153
更新日期:2008-04-11 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.6.1190
更新日期:1989-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.51.5.614
更新日期:1982-11-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh2001.097691
更新日期:2001-10-12 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.res.0000029784.15893.10
更新日期:2002-08-23 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.3.297
更新日期:1997-09-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.48.4.510
更新日期:1981-04-01 00:00:00
abstract::Growing evidence exists that ATP-sensitive mitochondrial potassium channels (MitoKATP channel) are a major contributor to the cardiac protection against ischemia. Given the importance of mitochondria in the cardiac cell, we tested whether the potent and specific opener of the MitoKATP channel diazoxide attenuates the ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.10.1156
更新日期:1999-05-28 00:00:00
abstract:RATIONALE:The low-density lipoprotein (LDL) receptor (LDLR) is a central determinant of circulating LDL-cholesterol and as such subject to tight regulation. Recent studies and genetic evidence implicate the inducible degrader of the LDLR (IDOL) as a regulator of LDLR abundance and of circulating levels of LDL-cholester...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.307298
更新日期:2016-02-05 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.4.693
更新日期:1988-10-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.306993
更新日期:2015-08-28 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.120.316943
更新日期:2020-10-09 00:00:00
abstract::The pulmonary vein is sleeved by myocardium, which is a major source of atrial fibrillation and is involved in congenital sinus venosus defects. Little is known about the cellular origin and mechanism of formation of the pulmonary myocardium. We observed a biphasic process of pulmonary myocardium formation in mice. Fi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.161182
更新日期:2007-10-26 00:00:00
abstract::We administered ascitic fluid containing atrial natriuretic factor (ANF) monoclonal antibody to rats after 3 weeks of exposure to hypoxia while the rats were still hypoxic. In additional chronically hypoxic rats, we infused synthetic rat ANF. In conscious chronically instrumented rats, after a bolus dose of 5 microgra...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.1.184
更新日期:1992-01-01 00:00:00
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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
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.311049
更新日期:2017-05-12 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.4.486
更新日期:1985-04-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000261352.81736.37
更新日期:2007-03-30 00:00:00
abstract::Cardiomyocyte hypertrophy is transcriptionally controlled and inhibited by glycogen synthase kinase 3beta (GSK3beta). Myocardin is a muscle-specific transcription factor with yet unknown relation to hypertrophy. Therefore, we investigated whether myocardin is sufficient to induce cardiomyocyte hypertrophy and whether ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000184684.88750.FE
更新日期:2005-09-30 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.4.606
更新日期:1985-04-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.2.437
更新日期:1988-08-01 00:00:00
abstract::Understanding molecular mechanisms regulating angiogenesis may lead to novel therapies for ischemic disorders. Hypoxia-inducible factor 1 (HIF-1) activates vascular endothelial growth factor (VEGF) gene expression in hypoxic/ischemic tissue. In this study we demonstrate that exposure of primary cultures of cardiac and...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000102937.50486.1B
更新日期:2003-11-28 00:00:00
abstract::The regulation of mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK) was studied in freshly isolated adult rat heart preparations. In contrast to the situation in ventricular myocytes cultured from neonatal rat hearts, stimulation of MAPK activity by 1 mumol/L phorbol 12-myristate 13-acetate (PMA) was not c...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.5.932
更新日期:1994-11-01 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
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000268412.34364.50
更新日期:2007-05-25 00:00:00
abstract::Controversy exists regarding the mechanism by which catecholamines stimulate renin secretion in vivo. A sensitive rat kidney slice system was utilized to study the direct effects of adrenergic agonists and antagonists on renin release in vitro. Catecholamines were protected from degradation by the addition of ascorbic...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.37.3.318
更新日期:1975-09-01 00:00:00