Increased NAD(P)H Oxidase and Reactive Oxygen Species in Coronary Arteries After Balloon Injury

Abstract—Reactive oxygen species (ROS), produced by cellular constituents of the arterial wall, provide a signaling mechanism involved in vascular remodeling. Because adventitial fibroblasts are actively involved in coronary remodeling, we examined whether the changes in the redox state affect their phenotypic characteristics. To this end, superoxide anion production and NAD(P)H oxidase activity were measured in porcine coronary arteries in vivo, and the effect of ROS generation on adventitial fibroblast proliferation was examined in vitro. Superoxide production (SOD- and Tiron-inhibitable nitro blue tetrazolium [NBT] reduction) increased significantly within 24 hours after balloon-induced injury, with the product of NBT reduction present predominantly in adventitial fibroblasts. These changes were NAD(P)H oxidase–dependent, because diphenyleneiodonium (DPI) abolished superoxide generation (P<0.001). Furthermore, the injury-induced superoxide production was associated with augmented NAD(P)H oxidase activi...