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

Research output: Contribution to journalArticlepeer-review

214 Scopus citations

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 mice, but there was little difference in Tg mice compared with wild-type (WT) mice. Proliferation and migration were reduced in cultured Nox1 VSMCs and increased in Tg cells. Tg 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 cells. Overexpression of S3A, a constitutively active cofilin mutant, partially recovered reduced migration of Nox1 cells, suggesting that reduction in cofilin activity contributes to impaired migration of Nox1 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.

Original languageEnglish
Pages (from-to)480-487
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume29
Issue number4
DOIs
StatePublished - 1 Apr 2009

Keywords

  • Migration
  • NADPH oxidase 1
  • Neointima
  • Reactive oxygen species
  • Vascular smooth muscle

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