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


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.
Azumi
Hiroshi
H
Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Inoue
Nobutaka
N
Ohashi
Yoshitaka
Y
Terashima
Mitsuyasu
M
Mori
Takao
T
Fujita
Hideki
H
Awano
Kojiro
K
Kobayashi
Katsuya
K
Maeda
Kazumi
K
Hata
Katsuya
K
Shinke
Toshiro
T
Kobayashi
Seiichi
S
Hirata
Ken-ichi
K
Kawashima
Seinosuke
S
Itabe
Hiroyuki
H
Hayashi
Yoshitake
Y
Imajoh-Ohmi
Shinobu
S
Itoh
Hiroshi
H
Yokoyama
Mitsuhiro
M
D000787:Angina Pectoris / Q000201:enzymology* / Q000209:etiology / Q000473:pathology / Q000601:surgery*; D000789:Angina, Unstable / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000601:surgery; D017225:Atherectomy, Coronary / Q000379:methods*; D003324:Coronary Artery Disease / Q000150:complications / Q000201:enzymology / Q000601:surgery; D003331:Coronary Vessels / Q000737:chemistry / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D026901:Membrane Transport Proteins; D009247:NADH, NADPH Oxidoreductases / Q000502:physiology*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D008077:Lipoproteins, LDL; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D013481:Superoxides; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C086986:CYBA protein, human; C022709:superoxide-forming enzyme; D009252:NADPH Dehydrogenase