Upregulation of Nox-based NAD(P)H oxidases in restenosis after carotid injury.
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.
Szöcs
Katalin
K
Department of Medicine, Emory University, Atlanta, GA 30322, USA.
Lassègue
Bernard
B
Sorescu
Dan
D
Hilenski
Lula L
LL
Valppu
Liisa
L
Couse
Tracey L
TL
Wilcox
Josiah N
JN
Quinn
Mark T
MT
Lambeth
J David
JD
Griendling
Kathy K
KK
D000818:Animals; D020212:Carotid Artery Injuries / Q000378:metabolism*; D002404:Catheterization / Q000009:adverse effects; D002455:Cell Division; D003251:Constriction, Pathologic / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D026901:Membrane Transport Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000293:injuries / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D000074624:NADPH Oxidase 1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors; D017539:Tunica Intima / Q000166:cytology / Q000378:metabolism
D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C000614712:NOX1 protein, rat; C498911:Nox4 protein, rat; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase