Abstract:
AIMS:The discovery of a specific prorenin receptor (PRR) suggests a biological function of prorenin that is independent of angiotensin I production. In the present study, we investigated the role of PRR on smooth muscle cell (SMC) migration. METHODS AND RESULTS:PRR was expressed in human mammary arteries and in cultured human aortic SMCs. Prorenin induced SMC migration in a dose-dependent manner, as assessed by Boyden chamber chemotaxis assay, and increased SMC random motility, as determined by video microscopy. The prorenin decoy peptide inhibited SMC migration in response to prorenin, and knockdown of PRR by small interfering RNA completely inhibited the migratory response to prorenin, demonstrating that the chemotactic action of prorenin is mediated by the PRR. Prorenin induced cytoskeleton reorganization and lamellipodia formation and increased the intracellular levels of both RhoA-GTP and Rac1-GTP through PRR. These effects were required for SMC migration, because the suppression by small interfering RNA of either Rac1 or RhoA GTP-bound forms completely blocked the PRR-mediated chemotactic effect. Prorenin also induced the formation of larger focal adhesions and cleavage of the focal adhesion kinase (pp125(FAK)) into two main fragments with molecular weights of 50 and 90 kDa. The generation of these two fragments of pp125(FAK) was reduced by the calpain inhibitor ALLN, which also inhibited SMC migration in response to prorenin. CONCLUSIONS:These results demonstrate that prorenin is a chemotactic factor for human aortic SMCs expressing PRR. This effect is elicited through reorganization of the cytoskeleton and focal adhesion, activation of RhoA and Rac1, and calpain-mediated cleavage of pp125(FAK).
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Greco CM,Camera M,Facchinetti L,Brambilla M,Pellegrino S,Gelmi ML,Tremoli E,Corsini A,Ferri Ndoi
10.1093/cvr/cvs204subject
Has Abstractpub_date
2012-08-01 00:00:00pages
366-74issue
3eissn
0008-6363issn
1755-3245pii
cvs204journal_volume
95pub_type
杂志文章abstract:BACKGROUND:A recent genome-wide association study identified a susceptibility locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for a small conductance calcium-activated potassium channel, we hypothesized that overexpression of the SK3 channel increases susceptibility to cardiac arrhythmias....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt269
更新日期:2014-02-01 00:00:00
abstract::Having an apparently healthy, thriving infant fail to reach his/her first birthday is profoundly tragic. This tragedy is compounded when the infant's death is unexpected and unexplained, signed out as sudden infant death syndrome (SIDS). Despite impressive success and welcome reductions in these tragic deaths due in l...
journal_title:Cardiovascular research
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abstract::Cardiovascular diseases are among the main causes of morbidity and mortality in Western countries and considered as a leading public health issue. Therefore, there is a strong need for new disease models to support the development of novel therapeutics approaches. The successive improvement of genome editing tools wit...
journal_title:Cardiovascular research
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journal_title:Cardiovascular research
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doi:10.1016/j.cardiores.2007.04.006
更新日期:2007-08-01 00:00:00
abstract::Oxygen-derived free radicals are thought to contribute to the initiation and progression of cardiovascular disease via several different mechanisms, such as consumption of nitric oxide, oxidation of proteins and lipids, and activation of redox-sensitive signalling cascades. Vascular NADPH oxidases are important source...
journal_title:Cardiovascular research
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更新日期:2005-01-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章,随机对照试验
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abstract:Aims:Sirtuin 3 (Sirt3) is a mitochondrial, nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase that reduces oxidative stress by activation of superoxide dismutase 2 (SOD2). Oxidative stress enhances arterial thrombosis. This study investigated the effects of genetic Sirt3 deletion on arterial thrombosis in m...
journal_title:Cardiovascular research
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::Coronary microvascular dysfunction (CMD) is commonly present in patients with metabolic derangements and is increasingly recognized as an important contributor to myocardial ischaemia, both in the presence and absence of epicardial coronary atherosclerosis. The latter condition is termed 'ischaemia and no obstructive ...
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更新日期:1996-12-01 00:00:00
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journal_title:Cardiovascular research
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更新日期:2006-05-01 00:00:00
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journal_title:Cardiovascular research
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doi:10.1093/cvr/cvu033
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
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doi:10.1093/cvr/cvn159
更新日期:2008-10-01 00:00:00
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更新日期:2004-03-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章,评审
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更新日期:1997-04-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00466-8
更新日期:2003-09-01 00:00:00
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更新日期:2011-01-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00225-3
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更新日期:1999-09-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv204
更新日期:2015-10-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/17.10.627
更新日期:1983-10-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.4.294
更新日期:1986-04-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.05.006
更新日期:2005-09-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.2.279
更新日期:1993-02-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.6.463
更新日期:1991-06-01 00:00:00
abstract::Major advances in molecular biology over the past decade have increased our understanding of how genes are expressed and regulated in mammalian cells in vivo. This knowledge has been translated to investigations of the molecular and cellular biology of the cardiovascular system. Gene transfer, the introduction of a re...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/28.4.445
更新日期:1994-04-01 00:00:00
abstract:OBJECTIVE:Despite the frequent use of anti-arrhythmic drugs in the general population, the electrophysiologic effects of these agents have not been elucidated in congestive heart failure (CHF). METHODS:To examine the impact of left ventricular dysfunction on actions of type III anti-arrhythmic drugs, we evaluated the ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00235-2
更新日期:2001-01-01 00:00:00