Abstract 900: Impact of NAD(P)H Oxidase-Derived Reactive Oxygen Species on Coronary Arterial Remodeling - A Comparative Intravascular Ultrasound and Histochemical Analysis of Atherosclerotic Lesions
Background: Coronary arterial remodeling, which is a response to the growth of atherosclerotic plaques, has been shown to be associated with plaque vulnerability. On the other hand, oxidative stress induced by reactive oxygen species (ROS) via NAD(P)H oxidase in the vasculature plays a crucial role in the pathogenesis of atherosclerosis-based cardiovascular diseases. In this study, the relationship between coronary arterial remodeling and ROS generation was examined by comparing pre-interventional intravascular ultrasound (IVUS) findings of atherosclerotic lesions to the histochemical findings of the corresponding specimens obtained by directional coronary atherectomy (DCA).
Methods and Results: Pre-DCA IVUS images of 29 patients were analyzed. Remodeling index was obtained by dividing the target-lesion external elastic membrane cross sectional area (EEM-CSA) by the reference-segment EEM-CSA. Expansive remodeling was defined as remodeling index > 1.0. 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 to total surface area in each specimen. ROS generation in lesions with expansive remodeling was significantly greater than that without remodeling (0.16 ± 0.09 vs 0.03 ± 0.02, p<0.0001), accompanied with a tendency of higher p22phox expression in lesions with expansive remodeling. Both ROS generation and p22phox expression were significantly correlated with IVUS-derived remodeling index (r=0.79, p<0.0001, r=0.44, p=0.017, respectively).
Conclusions: Upon comparison of IVUS and histochemical analyses, NAD(P)H oxidase-derived ROS was found to play a significant role in the coronary arterial remodeling process associated with plaque vulnerability in this study.