| Project/Area Number |
12470154
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
YOKOYAMA Mitsuhiro Kobe University, Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Professor, 医学部・附属病院, 教授 (40135794)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Nobutaka Kobe University, Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Assistant Professor, 大学院・医学系研究科, 助手 (10304099)
KAWASHIMA Seinosuke Kobe University, Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10177678)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2001: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2000: ¥8,800,000 (Direct Cost: ¥8,800,000)
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| Keywords | superoxide / atherosclerosis / glutathione peroxidase / NADH / NADPH oxidase / coronary artery disease / oxidized LDL / 冠動脈 / 免疫染色法 / NO合成酵素 / NADH oxidase |
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| Research Abstract |
Oxidative stress induced by reactive oxygen species (ROS) is implicated in the pathogenesis of a variety of vascular diseases including atherosclerosis and coronary artery disease. NADH/NADPH oxidase is an important source of reactive oxygen species (ROS).
Recently, we demonstrated that p22^<phox>, an essential component of this oxidase, was expressed in human coronary arteries, and its expression was enhanced with the progression of atherosclerosis. The present study was undertaken to investigate the functional importance of NADH/NADPH oxidase in pathogenesis of various vascular diseases.
We examined the effect of lysophosphatidylcholine (LPC), atherogenic component of oxidized LDL, on the activity of NADH/NADPH oxidase in cultured endthelial cells. Homogenates of cultured aortic endothelial cell had the enzymatic activity of NADH/NADPH. LPC induced O_2-generation. Thus the production of O_2-in endothelial cells is mainly mediated by the NADH/NADPH oxidase system and LPC activates this oxidase to enhance O_2-production.
The functional role of NADH/NADPH oxidase in pathpgenesis of atherosclerotic corbriary disease was investigated. For this aim, the expression of p22^<phox>, distribution of oxidized LDL and generation of ROS in directional coronary atherectomy (DCA) specimens were examined. DCA specimens were obtained from patients with stable (SAP) or unstable angina pectoris (UAP). ROS generation was closely associated, with the distribution of p22^<phox> and oxidized LDL. There was a correlation between ROS and the expression of p22^<phox> or oxidized LDL. These factors of UAP were significantly higher compared with SAP. ROS generated by p22^<pfox> -based NADH/NADPH oxidase likely mediate oxidative modification of LDL, and it might play a major role in pathogenesis of atherosclerotic coronary artery disease.
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