| Project/Area Number |
14370230
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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 | HOKKAIDO UNIVERSITY (2004)
Kyushu University (2002-2003) |
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Principal Investigator |
TSUTSUI Hiroyuki Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (70264017)
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| Co-Investigator(Kenkyū-buntansha) |
TADA Hideo Kyushu University Hospital, Adju.Assis.Prof., 九州大学病院, 助手
KUBOTA Toru Kyushu Univ., Grad.School of Med., Adju.Assis.Prof., 大学院・医学研究院, 助手 (40325444)
UTSUMI Hideo Kyushu Univ., Grad.School of Pharm.Sciences, Prof., 薬学研究院, 教授 (20101694)
KANG Dongchong Kyushu University Hospital, Asso.Prof., 九州大学病院, 助教授 (80214716)
中別府 雄作 九州大学, 生体防御医学研究所, 教授 (30180350)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2004: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2002: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | Heart failure / Mitochondria / DNA / Electron transport complex / ROS / Cytokine / Myocyte / Oxidative stress / ミトコンドア |
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| Research Abstract |
Previous basic, clinical, population sciences have advanced the modern treatment of HF. However, its efficacy is still limited. An important approach to solve this crucial issue is the development of novel therapeutic strategies based on a novel insight into the pathophysiology of myocardial remodeling and failure. Our approach is to develop the therapeutic strategy by regulating mitochondrial oxidative stress. In the failing hearts, oxygen radicals are produced by the defects of mitochondrial electron transport. They cause mitochondrial DNA damage and functional decline, leading to the further production of oxygen radicals. Oxidative stress causes myocyte hypertrophy, apoptosis, and interstitial fibrosis by activating matrix metalloproteinases, all of which result in myocardial remodeling and failure. Therefore, mitochondrial oxidative stress and DNA damage are good therapeutic targets. Oxidative stress is involved not only in HF, but also in various cardiovascular diseases including atherosclerosis and hypertension. Therefore, therapeutic strategies to modulate this maladaptive response should definitely become a target for future extensive investigation and therapies designed to interfere with oxidative stress, especially within the mitochondria, could have a broader application.
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