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Original Articles

Impact of NAD(P)H Oxidase-Derived Reactive Oxygen Species on Coronary Arterial Remodeling

A Comparative Intravascular Ultrasound and Histochemical Analysis of Atherosclerotic Lesions

Mitsuyasu Terashima, MD; Yoshitaka Ohashi, MD; Hiroshi Azumi, MD; Kazunori Otsui, MD; Hideaki Kaneda, MD; Kojiro Awano, MD; Seiichi Kobayashi, MD; Tomoyuki Honjo, MD; Takahiko Suzuki, MD; Kazumi Maeda, MD; Mitsuhiro Yokoyama, MD and Nobutaka Inoue, MD

From the Toyohashi Heart Center (M.T., T.S.), Toyohashi, Japan; Miki City Hospital (Y.O., K.A., T.H., K.M.), Miki, Japan; Kobe University Graduate School of Medicine (H.A., S.K., M.Y.), Kobe, Japan; National Cardiovascular Center Research Institute (K.O.), Suita, Japan; Okinaka Memorial Institute for Medical Research (H.K.), Tokyo, Japan; and Kobe Rosai Hospital (N.I.), Kobe, Japan.

Correspondence to Mitsuyasu Terashima, MD, Toyohashi Heart Center, 21-1 Gobudori, Oyama-cho, Toyohashi 441-8530, Japan. E-mail mterashima-circ{at}umin.ac.jp

Received June 20, 2008; accepted March 2, 2009.

Background— Coronary arterial remodeling, which is a response to the growth of atherosclerotic plaques, is associated with plaque vulnerability. Oxidative stress induced by reactive oxygen species (ROS) via NAD(P)H oxidase in the vasculature also plays a crucial role in the pathogenesis of atherosclerosis-based cardiovascular disease. In this study, the relationship between coronary arterial remodeling and ROS generation was examined by comparing preinterventional intravascular ultrasound findings of atherosclerotic lesions to the histochemical findings of corresponding specimens obtained by directional coronary atherectomy.

Methods and Results— Predirectional coronary atherectomy intravascular ultrasound images of 49 patients were analyzed. The remodeling index was calculated by dividing the target-lesion external elastic membrane cross-sectional area by the reference-segment external elastic membrane cross-sectional area. Expansive remodeling was defined as a remodeling index of >1.0. ROS generation and NAD(P)H oxidase p22^phox expression in directional coronary atherectomy specimens were evaluated using the dihydroethidium staining method and immunohistochemistry as the ratio of the positive area to the total surface area in each specimen, respectively. ROS generation and p22^phox expression were significantly greater in lesions with expansive remodeling than in lesions without remodeling (0.18±0.12 versus 0.03±0.02, P<0.0001, 0.10±0.08 versus 0.04±0.05, P=0.0039, respectively). Both ROS generation and p22^phox expression significantly correlated with the intravascular ultrasound-derived remodeling index (r=0.77, P<0.0001, r=0.53, P<0.0001, respectively).

Conclusions— Simultaneous examination with intravascular ultrasound and immunohistochemistry analyses suggests that NAD(P)H oxidase-derived ROS is related to the coronary arterial remodeling process associated with plaque vulnerability.

Key Words: atherosclerosis • remodeling • intravascular ultrasound • reactive oxygen species • oxidative stress

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