Superoxide generation in directional coronary atherectomy specimens of patients with angina pectoris: important role of NAD(P)H oxidase.

Abstract

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.

• Authors: 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
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 22 Issue 11 Pg. 1838-44 (Nov 01 2002) ISSN: 1524-4636 [Electronic] United States
• PMID: 12426213 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipoproteins, LDL
• Membrane Transport Proteins
• Phosphoproteins
• Reactive Oxygen Species
• oxidized low density lipoprotein
• Superoxides
• NADH, NADPH Oxidoreductases
• NADPH Oxidases
• CYBA protein, human
• superoxide-forming enzyme
• NADPH Dehydrogenase

Topics

• Angina Pectoris (enzymology, etiology, pathology, surgery)
• Angina, Unstable (enzymology, etiology, pathology, surgery)
• Atherectomy, Coronary (methods)
• Coronary Artery Disease (complications, enzymology, surgery)
• Coronary Vessels (chemistry, enzymology, pathology, surgery)
• Humans
• Lipoproteins, LDL (metabolism)
• Membrane Transport Proteins
• NADH, NADPH Oxidoreductases (physiology)
• NADPH Dehydrogenase (metabolism)
• NADPH Oxidases
• Phosphoproteins (metabolism)
• Reactive Oxygen Species (metabolism)
• Superoxides (metabolism)