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Selective Involvement of Serum Response Factor in Pressure-Induced Myogenic Tone in Resistance Arteries.
MedLine Citation:
PMID:  23264443     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: In resistance arteries, diameter adjustment in response to pressure changes depends on the vascular cytoskeleton integrity. Serum response factor (SRF) is a dispensable transcription factor for cellular growth, but its role remains unknown in resistance arteries. We hypothesized that SRF is required for appropriate microvascular contraction. METHODS AND RESULTS: We used mice in which SRF was specifically deleted in smooth muscle or endothelial cells, and their control. Myogenic tone and pharmacological contraction was determined in resistance arteries. mRNA and protein expression were assessed by quantitative real-time PCR (qRT-PCR) and Western blot. Actin polymerization was determined by confocal microscopy. Stress-activated channel activity was measured by patch clamp. Myogenic tone developing in response to pressure was dramatically decreased by SRF deletion (5.9±2.3%) compared with control (16.3±3.2%). This defect was accompanied by decreases in actin polymerization, filamin A, MLCK and MLC expression level, and stress-activated channel activity and sensitivity in response to pressure. Contractions induced by phenylephrine or U46619 were not modified, despite a higher sensitivity to p38 blockade; this highlights a compensatory pathway, allowing normal receptor-dependent contraction. CONCLUSIONS: This study shows for the first time that SRF has a major part to play in the control of local blood flow via its central role in pressure-induced myogenic tone in resistance arteries.
Authors:
Kevin Retailleau; Bertrand Toutain; Guillaume Galmiche; Céline Fassot; Reza Sharif-Naeini; Gilles Kauffenstein; Mathias Mericskay; Fabrice Duprat; Linda Grimaud; Jean Merot; Aurelie Lardeux; Anne Pizard; Véronique Baudrie; Xavier Jeunemaitre; Robert Feil; Joachim R Göthert; Patrick Lacolley; Daniel Henrion; Zhenlin Li; Laurent Loufrani
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-20
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  -     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
CNRS UMR-6214, INSERM U1083, Université d'Angers, PRES LUNAM, Angers, France.
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