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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1838.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Superoxide Generation in Directional Coronary Atherectomy Specimens of Patients With Angina Pectoris

Important Role of NAD(P)H Oxidase

Hiroshi Azumi; Nobutaka Inoue; Yoshitaka Ohashi; Mitsuyasu Terashima; Takao Mori; Hideki Fujita; Kojiro Awano; Katsuya Kobayashi; Kazumi Maeda; Katsuya Hata; Toshiro Shinke; Seiichi Kobayashi; Ken-ichi Hirata; Seinosuke Kawashima; Hiroyuki Itabe; Yoshitake Hayashi; Shinobu Imajoh-Ohmi; Hiroshi Itoh; Mitsuhiro Yokoyama

From the Division of Cardiovascular and Respiratory Medicine, Departments of Internal Medicine (H.A., N.I., K.H., T.S., K.H., S. Kawashima, M.Y.) and Surgical Pathology (S. Kobayashi, Y.H., H. Ito), Kobe University Graduate School of Medicine, Kobe, Japan; Cardiology Division, Miki City Hospital (Y.O., M.T., T.M., H.F., K.A., K.K., K.M.), Miki, Japan; The Institute of Medical Science, University of Tokyo (S.I.-O), Tokyo, Japan; and the Faculty of Pharmaceutical Sciences, Teikyo University (H. Itabe), Kanagawa, Japan.

Correspondence to Nobutaka Inoue, MD, PhD, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, chuo-ku, Kobe 650-0017, Japan. E-mail nobutaka{at}med.kobe-u.ac.jp

Objective— NADH/NADPH oxidase is an important source of reactive oxygen species (ROS) in the vasculature. Recently, we demonstrated that p22^phox, an essential component of this oxidase, was expressed in human coronary arteries and that its expression was enhanced with the progression of atherosclerosis. The present study was undertaken to investigate its functional importance in the pathogenesis of coronary artery disease. For this aim, the expression of p22^phox, the distribution of oxidized low density lipoprotein (LDL), and the generation of ROS in directional coronary atherectomy (DCA) specimens were examined.

Methods and Results— DCA specimens were obtained from patients with stable or unstable angina pectoris. The distribution of p22^phox and of oxidized LDL was examined by immunohistochemistry. The generation of superoxide in DCA specimens was assessed by the dihydroethidium method and lucigenin-enhanced chemiluminescence. ROS were closely associated with the distribution of p22^phox and oxidized LDL. Not only inflammatory cells but also smooth muscle cells and fibroblasts generated ROS. There was a correlation between ROS and the expression of p22^phox or oxidized LDL. The generation of ROS was significantly higher in unstable angina pectoris compared with stable angina pectoris.

Conclusions— ROS generated by p22^phox-based NADH/NADPH oxidase likely mediate the oxidative modification of LDL and might play a major role in pathogenesis of atherosclerotic coronary artery disease.

Key Words: atherosclerosis • free radicals • coronary disease

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