Journal article
Inactivation of Serum Response Factor Contributes To Decrease Vascular Muscular Tone and Arterial Stiffness in Mice
Circulation research, Vol.112(7), pp.1035-U149
03/2013
DOI: 10.1161/CIRCRESAHA.113.301076
PMID: 23426017
Abstract
Rationale: Vascular smooth muscle (SM) cell phenotypic modulation plays an important role in arterial stiffening associated with aging. Serum response factor (SRF) is a major transcription factor regulating SM genes involved in maintenance of the contractile state of vascular SM cells. Objective: We investigated whether SRF and its target genes regulate intrinsic SM tone and thereby arterial stiffness. Methods and Results: The SRF gene was inactivated SM-specific knockout of SRF (SRFSMKO) specifically in vascular SM cells by injection of tamoxifen into adult transgenic mice. Fifteen days later, arterial pressure and carotid thickness were lower in SRFSMKO than in control mice. The carotid distensibility/pressure and elastic modulus/wall stress curves showed a greater arterial elasticity in SRFSMKO without modification in collagen/elastin ratio. In SRFSMKO, vasodilation was decreased in aorta and carotid arteries, whereas a decrease in contractile response was found in mesenteric arteries. By contrast, in mice with inducible SRF overexpression, the in vitro contractile response was significantly increased in all arteries. Without endothelium, the contraction was reduced in SRFSMKO compared with control aortic rings owing to impairment of the NO pathway. Contractile components (SM-actin and myosin light chain), regulators of the contractile response (myosin light chain kinase, myosin phosphatase target subunit 1, and protein kinase C-potentiated myosin phosphatase inhibitor) and integrins were reduced in SRFSMKO. Conclusions: SRF controls vasoconstriction in mesenteric arteries via vascular SM cell phenotypic modulation linked to changes in contractile protein gene expression. SRF-related decreases in vasomotor tone and cell-matrix attachment increase arterial elasticity in large arteries. (Circ Res. 2013;112:1035-1045.)
Details
- Title: Subtitle
- Inactivation of Serum Response Factor Contributes To Decrease Vascular Muscular Tone and Arterial Stiffness in Mice
- Creators
- Guillaume Galmiche - BernardCarlos Labat - InsermMathias Mericskay - BernardKarima Ait Aissa - InsermJocelyne Blanc - BernardKevin Retailleau - InsermMustapha Bourhim - InsermDario Coletti - Case Western Reserve UniversityLaurent Loufrani - InsermJacqueline Gao-Li - BernardRobert Feil - University of TübingenPascal Challande - Institut Jean Le Rond d'AlembertDaniel Henrion - Université d'AngersJean-Franois Decaux - Institut CochinVéronique Regnault - InsermPatrick Lacolley - InsermZhenlin Li - Case Western Reserve University
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.112(7), pp.1035-U149
- Publisher
- American Heart Association
- DOI
- 10.1161/CIRCRESAHA.113.301076
- PMID
- 23426017
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 03/2013
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984359792802771
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