| Project/Area Number |
17390223
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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 |
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Principal Investigator |
TSUTSUI Hiroyuki Hokkaido University, Graduate School of Medicine, Professor (70264017)
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| Co-Investigator(Kenkyū-buntansha) |
MIWA Soichi Hokkaido University, Graduate School of Medicine, Professor (40157706)
CHIBA Hitoshi Hokkaido University, School of Medicine, Professor (70197622)
KANG Dongchon Kyusyu University, Graduate School of Medicine Sciences, Professor (80214716)
ICHIKAWA Kazuhiro Kyusyu University, Graduate School of Pharmaceutical Sciences, Professor (10271115)
ISHIMORI Naoki Hokkaido University, Graduate University Hospital, Assistant Professor (70399848)
藤井 聡 名古屋市立大学, 大学院薬学研究科, 教授 (90291228)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,400,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2007: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2006: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2005: ¥7,100,000 (Direct Cost: ¥7,100,000)
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| Keywords | Mitochondria / Transcription factor / Genes / Mitochondrial DNA / Oxidative stress / Cardiovascular diseases / Hypertension / Heart failure / 糖尿病 / 内科 / 細胞・組織 / 循環器・高血圧 |
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| Research Abstract |
Recent experimental and clinical studies have suggested that oxidative stress is enhanced in heart failure. The production of oxygen radicals is increased in the failing heart whereas antioxidant enzyme activities are preserved normal. Mitochondrial electron transport is an enzymatic source of oxygen radical generation and also a target against oxidant-induced damage in the failing myocardium. Chronic increases in oxygen radical production in the mitochondria can lead to a catastrophic cycle of mitochondrial DNA damage as well as functional decline, further oxygen radical generation, and cellular injury. Reactive oxygen species induce myocyte hypertrophy, apoptosis, and interstitial fibrosis by activating matrix metalloproteinases. These cellular events play an important role in the development and progression of maladaptive cardiac remodeling and failure. Therefore, oxidative stress and mitochondrial DNA damage are good therapeutic targets. Overexpression of peroxiredoxin-3 (Prx-3), mitochondrial antioxidant, or mitochondrial transcription factor A (TFAM) could ameliorate the decline in mitochondrial DNA copy number in failing hearts. Consistent with alterations in mitochondrial DNA, the decrease in oxidative capacities was also prevented. Therefore, the activation of peroxiredoxin-3 or TFAM expression could ameliorate the pathophysiological processes seen in myocardial failure. Inhibition of oxidative stress and mitochondrial DNA damage could be the novel and potentially effective treatment strategies for various cardiovascular diseases including heart failure.
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