TY - JOUR
T1 - Mechanisms of vascular smooth muscle NADPH oxidase 1 (Nox1) contribution to injury-induced neointimal formation
AU - Lee, Moo Yeol
AU - Martin, Alejandra San
AU - Mehta, Puja K.
AU - Dikalova, Anna E.
AU - Garrido, Abel Martin
AU - Datla, S. Raju
AU - Lyons, Erin
AU - Krause, Karl Heinz
AU - Banfi, Botond
AU - Lambeth, J. David
AU - Lassègue, Bernard
AU - Griendling, Kathy K.
PY - 2009/4/1
Y1 - 2009/4/1
N2 - 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.
AB - 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.
KW - Migration
KW - NADPH oxidase 1
KW - Neointima
KW - Reactive oxygen species
KW - Vascular smooth muscle
UR - http://www.scopus.com/inward/record.url?scp=63449105018&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.108.181925
DO - 10.1161/ATVBAHA.108.181925
M3 - Article
C2 - 19150879
AN - SCOPUS:63449105018
SN - 1079-5642
VL - 29
SP - 480
EP - 487
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 4
ER -