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Author Notes:

Correspondence: Kathy K. Griendling, Ph.D. Emory University School of Medicine Division of Cardiology 319 WMB, 1639 Pierce Dr. Atlanta, GA 30322, USA Phone: 404-727-3364 Fax: 404-727-3585 Email: kgriend@emory.edu

Present address: College of Pharmacy, Chonnam National University, Gwangju, 500-757, Korea

We are grateful to Dr. John Condeelis for providing the S3A plasmid.

Disclosures: None.


Research Funding:

This work was supported by NIH grants HL38206, HL093115 and HL058863, and American Heart Association fellowship #0525465B to ASM.

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

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Journal Title:

Arteriosclerosis, Thrombosis, and Vascular Biology


Volume 29, Number 4


, Pages 480-487

Type of Work:

Article | Post-print: After Peer Review


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 Nox1y/- mice, but there was little difference in TgSMCnox1 mice compared with wild type (WT) mice. Proliferation and migration were reduced in cultured Nox1y/- VSMCs and increased in TgSMCnox1 cells. TgSMCnox1 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 Nox1y/- cells. Overexpression of S3A, a constitutively active cofilin mutant, partially recovered reduced migration of Nox1y/- cells, suggesting that reduction in cofilin activity contributes to impaired migration of Nox1y/- 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.

Copyright information:

© 2009 American Heart Association, Inc. All rights reserved.

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