Journal article
Mechanisms of Vascular Smooth Muscle NADPH Oxidase 1 (Nox1) Contribution to Injury-Induced Neointimal Formation
Arteriosclerosis, thrombosis, and vascular biology, Vol.29(4), pp.480-487
04/01/2009
DOI: 10.1161/ATVBAHA.108.181925
PMCID: PMC2734189
PMID: 19150879
Abstract
Objective-Vascular NADPH oxidases (Noxes) have been implicated in cardiovascular diseases; however, the importance of individual Nox homologues remains unclear. Here, the role of the vascular smooth muscle cell (VSMC) Nox1 in neointima formation was studied using genetically modified animal models.
Methods and Results-Wire injury-induced neointima formation in the femoral artery, along with proliferation and apoptosis, was reduced in Nox1(y/-) mice, but there was little difference in Tg(SMCnox1) mice compared with wild-type (WT) mice. Proliferation and migration were reduced in cultured Nox1(y/-) VSMCs and increased in Tg(SMCnox1) cells. Tg(SMCnox1) cells exhibited increased fibronectin secretion, but neither collagen I production nor cell adhesion was affected by alteration of Nox1. Using antibody microarray and Western blotting analysis, increased cofilin phosphorylation and mDia1 expression and decreased PAK1 expression were detected in Nox1(y/-) cells. Overexpression of S3A, a constitutively active cofilin mutant, partially recovered reduced migration of Nox1(y/-) cells, suggesting that reduction in cofilin activity contributes to impaired migration of Nox1(y/-) VSMCs.
Conclusions-These results indicate that Nox1 plays a critical role in neointima formation by mediating VSMC migration, proliferation, and extracellular matrix production, and that cofilin is a major effector of Nox1-mediated migration. Inhibition of Nox1 may be an efficient strategy to suppress neointimal formation. (Arterioscler Thromb Vasc Biol. 2009; 29: 480-487.)
Details
- Title: Subtitle
- Mechanisms of Vascular Smooth Muscle NADPH Oxidase 1 (Nox1) Contribution to Injury-Induced Neointimal Formation
- Creators
- Moo Yeol Lee - Emory UniversityAlejandra San MartinPuja K. MehtaAnna E. DikalovaAbel Martin GarridoS. Raju DatlaErin Lyons - Lippincott Williams & WilkinsKarl-Heinz Krause - Univ Geneva, Dept Pathol & Immunol, CH-1211 Geneva 4, SwitzerlandBotond Banfi - Univ Iowa, Dept Anat & Cell Biol, Roy J & Lucille A Carver Coll Med, Iowa City, IA USAJ. David Lambeth - Emory and Henry CollegeBernard Lasse GueKathy K. Griendling - Emory University
- Resource Type
- Journal article
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.29(4), pp.480-487
- Publisher
- Lippincott Williams & Wilkins
- DOI
- 10.1161/ATVBAHA.108.181925
- PMID
- 19150879
- PMCID
- PMC2734189
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Number of pages
- 8
- Grant note
- K99HL093115 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) HL38206; HL093115; HL058863 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 0525465B / American Heart Association
- Language
- English
- Date published
- 04/01/2009
- Academic Unit
- Anatomy and Cell Biology; Otolaryngology; Internal Medicine
- Record Identifier
- 9984284344302771
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