Upregulation of Nox-based NAD(P)H oxidases in restenosis after carotid injury

TY - JOUR

T1 - Upregulation of Nox-based NAD(P)H oxidases in restenosis after carotid injury

AU - Szöcs, Katalin

AU - Lassègue, Bernard

AU - Sorescu, Dan

AU - Hilenski, Lula L

AU - Valppu, Liisa

AU - Couse, Tracey L

AU - Wilcox, Josiah N

AU - Quinn, Mark T

AU - Lambeth, J David

AU - Griendling, Kathy K

PY - 2002/1

Y1 - 2002/1

N2 - 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.

AB - 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.

KW - Animals

KW - Carotid Artery Injuries/metabolism

KW - Catheterization/adverse effects

KW - Cell Division

KW - Constriction, Pathologic/metabolism

KW - Fibroblasts/metabolism

KW - Membrane Transport Proteins

KW - Muscle, Smooth, Vascular/cytology

KW - NADH, NADPH Oxidoreductases/metabolism

KW - NADPH Dehydrogenase/metabolism

KW - NADPH Oxidase 1

KW - NADPH Oxidase 4

KW - NADPH Oxidases/metabolism

KW - Phosphoproteins/metabolism

KW - RNA, Messenger/metabolism

KW - Rats

KW - Rats, Sprague-Dawley

KW - Superoxides/metabolism

KW - Time Factors

KW - Tunica Intima/cytology

U2 - 10.1161/hq0102.102189

DO - 10.1161/hq0102.102189

M3 - SCORING: Journal article

C2 - 11788456

VL - 22

SP - 21

EP - 27

JO - ARTERIOSCL THROM VAS

JF - ARTERIOSCL THROM VAS

SN - 1079-5642

IS - 1

ER -