This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 29/4/480    most recent ATVBAHA.108.181925v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, M. Y. Articles by Griendling, K. K. Search for Related Content PubMed PubMed Citation Articles by Lee, M. Y. Articles by Griendling, K. K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Substance via MeSH

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:480.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Mechanisms of Vascular Smooth Muscle NADPH Oxidase 1 (Nox1) Contribution to Injury-Induced Neointimal Formation

Moo Yeol Lee; Alejandra San Martin; Puja K. Mehta; Anna E. Dikalova; Abel Martin Garrido; S. Raju Datla; Erin Lyons; Karl-Heinz Krause; Botond Banfi; J. David Lambeth; Bernard Lassègue; Kathy K. Griendling

From the Department of Medicine, Division of Cardiology (M.Y.L., A.S.M., P.K.M., A.E.D., A.M.G., E.L., B.L., K.K.G.), and the Department of Pathology (J.D.L.), Emory University, Atlanta, Ga; the Department of Pathology and Immunology (K.-H.K.), University of Geneva, Switzerland; and the Department of Anatomy & Cell Biology (B.B.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City. Current address for M.Y.L.: College of Pharmacy, Chonnam National University, Gwangju, Korea.

Correspondence to Kathy K. Griendling, PhD, Emory University School of Medicine, Division of Cardiology, 319 WMB, 1639 Pierce Dr, Atlanta, GA 30322. E-mail kgriend{at}emory.edu

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.

The role of specific NADPH oxidase (Nox) proteins in vascular disease is incompletely understood. We show here 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.

Key Words: NADPH oxidase 1 • neointima • migration • vascular smooth muscle • reactive oxygen species

This article has been cited by other articles:

				F. J. Miller Jr NADPH Oxidase 4: Walking the Walk With Poldip2 Circ. Res., July 31, 2009; 105(3): 209 - 210. [Full Text] [PDF]

				A. N. Lyle, N. N. Deshpande, Y. Taniyama, B. Seidel-Rogol, L. Pounkova, P. Du, C. Papaharalambus, B. Lassegue, and K. K. Griendling Poldip2, a Novel Regulator of Nox4 and Cytoskeletal Integrity in Vascular Smooth Muscle Cells Circ. Res., July 31, 2009; 105(3): 249 - 259. [Abstract] [Full Text] [PDF]

				J.-S. Kim, T. Y. Huang, and G. M. Bokoch Reactive Oxygen Species Regulate a Slingshot-Cofilin Activation Pathway Mol. Biol. Cell, June 1, 2009; 20(11): 2650 - 2660. [Abstract] [Full Text] [PDF]