title: 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.
  
  
  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.affiliation: Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Azumi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Inoue
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Terashima
authors.forename: Takao
authors.initials: T
authors.lastname: Mori
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujita
authors.forename: Kojiro
authors.initials: K
authors.lastname: Awano
authors.forename: Katsuya
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Kazumi
authors.initials: K
authors.lastname: Maeda
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hata
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shinke
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Seinosuke
authors.initials: S
authors.lastname: Kawashima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Itabe
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Shinobu
authors.initials: S
authors.lastname: Imajoh-Ohmi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokoyama
mesh_terms: 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*
chemical_list: 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