Background: Oxidative stress induced by reactive oxygen species (ROS) in the vessel wall plays an essential role in atherogenesis. Recently, we demonstrated that the generation of ROS via NAD(P)H oxidase was correlated with plaque instability using coronary specimens obtained by directional coronary atherectomy (DCA). In this study, the relation between plaque formation and ROS generation was studied based on pre-interventional examination with intravascular ultrasound (IVUS) and histological analysis of the corresponding DCA specimens.
Methods: Pre-interventional IVUS images of 29 patients were analyzed. Vessel cross-sectional area (CSA), lumen CSA, plaque CSA and % plaque area were obtained at the minimal lumen site. ROS generation and expression of NAD(P)H oxidase p22phox in DCA specimens were evaluated by the dihydroethidium method and immunohistochemistry as the ratio of positive area versus total surface area in each specimen.
Results: ROS positive area ratio in DCA specimens was correlated positively with vessel CSA, plaque CSA, and % plaque area (r = 0.51, p = 0.0046; r = 0.62, p = 0.0004; r = 0.60, p = 0.0006, respectively). Further, p22phox positive area ratio in DCA specimens was also correlated with vessel CSA and plaque CSA (r = 0.47, p = 0.0095; r = 0.47, p = 0.0103, respectively).
Conclusions: This in vivo study clearly demonstrates that NAD(P)H oxidase-derived ROS plays a significant role in the development of atherosclerosis.