| Project/Area Number |
13670712
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 |
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)
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| Co-Investigator(Kenkyū-buntansha) |
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) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | NADH / NADPH oxidase / Coronary artery disease / SOD / Unstable plaque / thioredoxin / 酸化ストレス / 精神的ストレス / NADH / NADPH oxidase / 動脈硬化 |
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| Research Abstract |
[Background] Oxidative stress induced by reactive oxygen species (ROS) plays an important role in pathogenesis of ischemic heart disease. The redox state is determined by the balance between antioxidants and the ROS generating system. Against enhanced ROS, mammalian cells have a complex network of antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase. On the other hand, NAD (P) H oxidase is a major source of ROS in vascular cells. [Purpose] To clarify the role of oxidative stress in atherosclerotic vascular diseases, we investigated by immunohistoshemistry the expressional changes of antioxidative enzymes and NAD (P) H oxidase in coronary arteries specimens obtained from autopsied cases and directional coronary atherectomy (DCA). Furthermore, the influence of chronic mental stress on the redox state was examined using rat restrain-models. [Results] In nonatherosclerotic coronary arteries, Cu/Zn SOD and Mn SOD were expressed in medial smooth muscle cells (SMC), whereas cytosolic GPx (GPx-1) was expressed mainly in endothelium and weakly in medial SMC. Migrating SMCs and macrophages in atheromatous plaques expressed these antioxidative enzymes intensively. The generation of ROS in DCA specimens were closely associated with the distribution of NADH/NADPH oxidase p22^<phox> and oxidized LDL. There was a correlation between ROS and the expression of p22^<phox> or oxidized LDL. Chronic mental stress enhanced in vascular ROS generation in rat restrain-models. [Conclusion] The expression of antioxidant enzymes and the ROS generating system are dynamically regulated. Chronic mental stress induced their imbalance.
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