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Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:21-27
doi: 10.1161/hq0102.102189
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:21.)
© 2002 American Heart Association, Inc.


Vascular Biology

Upregulation of Nox-Based NAD(P)H Oxidases in Restenosis After Carotid Injury

Katalin Szöcs; Bernard Lassègue; Dan Sorescu; Lula L. Hilenski; Liisa Valppu; Tracey L. Couse; Josiah N. Wilcox; Mark T. Quinn; J.David Lambeth; Kathy K. Griendling

From the Department of Medicine (K.S., B.L., D.S., L.L.H., L.V., K.K.G.), Division of Cardiology, the Winship Cancer Institute (T.L.C., J.N.W.), Division of Hematology/Oncology, and the Department of Biochemistry (J.D.L.), Emory University, Atlanta, Ga, and the Department of Veterinary Molecular Biology (M.T.Q.), Montana State University, Bozeman.

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

Restenosis, a frequent complication of coronary angioplasty, is associated with increased superoxide (O2·-) production. Although the molecular identity of the responsible oxidase is unclear, an NAD(P)H oxidase appears to be involved. In smooth muscle, p22phox and 2 homologues of gp91phox, nox1 and nox4, are expressed, whereas fibroblasts contain gp91phox. To begin investigating the possibility that these oxidase components might contribute to the increased O2·- that accompanies neointimal formation, we measured their expression after balloon injury of the rat carotid artery. The increase in O2·- production 3 to 15 days after surgery was not due to inflammatory cell infiltration but appeared to be derived from medial and neointimal smooth muscle cells and adventitial fibroblasts. Nox1 and p22phox mRNAs were increased 2.7- and 3.6-fold, respectively, at day 3 after injury and remained elevated for 15 days. gp91Phox was increased 7 to 15 days after injury, and nox4 expression was increased 2-fold, but only at day 15 after surgery. These results confirm and extend our previous in vitro data and suggest that in the vasculature, the nox-based NAD(P)H oxidases serve different functions. This dynamic regulation of oxidase components may be critical to smooth muscle phenotypic modulation in restenosis and atherosclerosis.


Key Words: neointimal formation • superoxide • NAD(P)H oxidase • balloon injury • nox




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