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CYCLIC STRETCH-INDUCED THROMBIN GENERATION BY RAT VASCULAR SMOOTH MUSCLE CELLS IS MEDIATED BY THE INTEGRIN αVβ3 PATHWAY.
MedLine Citation:
PMID:  22915765     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: Vascular smooth muscle cell (VSMC) phenotypic modulation plays a pivotal role in atherothrombotic diseases. Thrombin generation at the surface of VSMCs and activation of integrin mechanotransduction pathways represent potential mechanisms. Here, we examine whether mechanical stretch increases thrombin generation on cultured rat aortic VSMCs.Methods and ResultsThe integrin α(v)β(3) antagonist peptide (cRGDPV) dose-dependently decreased thrombin generation without stretch. Static stretch (5%, 1 Hz) failed to modify the thrombin-forming capacity of VSMCs whereas 10% cyclic stretch during 60 and 360 min enhanced integrin α(v)β(3) expression and thrombin generation at the surface of VSMCs by 30% without inducing apoptosis. Cyclic stretch also stimulated Src phosphorylation, cleavage of talin and binding of prothrombin to VSMCs. Upregulation of α(v)β(3) expression, Src phosphorylation and enhanced thrombin generation by cyclic stretch were abolished by cRGDPV and siRNA against α(v) as well as by selective inhibition of integrin α(v)β(3) inside-out signaling by a talin-siRNA. Complete abolition of stretch-induced VSMC-supported thrombin generation by the RGT peptide, which disrupts the interaction of Src with the β(3) cytoplasmic tail, demonstrates the link between outside-in pathways involving β(3)-Src interaction and thrombin activity dependent on inside-out signaling. CONCLUSION: These data show that the contribution of cyclic stretch to VSMC-supported thrombin generation is driven by the integrin α(v)β(3) signaling pathway, and suggest a role for pulsatility-induced intramural thrombin in VSMC-dependent vascular remodeling.
Authors:
Xianqing Mao; Rose Said; Huguette Louis; Jean-Pierre Max; Mustapha Bourhim; Pascal Challande; Denis Wahl; Zhenlin Li; Veronique Regnault; Patrick Lacolley
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-21
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
INSERM, U961, Vandoeuvre-les-Nancy, France.
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