2004 Fiscal Year Final Research Report Summary
Role of oxidative mitochondrial DNA damage and its preventive mechanisms in the development and progression of heart failure
| 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)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Heart failure / Mitochondria / DNA / Electron transport complex / ROS / Cytokine / Myocyte / Oxidative stress |
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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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Research Products
(28 results)
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[Journal Article] Overexpression of tumor necrosis factor-alpha increases production of hydroxyl radical in murine myocardium.2003
Author(s)
Machida Y, Kubota T, Kawamura N, Funakoshi H, Ide T, Utsumi H, Li YY, Feldman AM, Tsutsui H, Shimokawa H, Takeshita A.
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Journal Title
Am J Physiol Heart Circ Physiol. 284
Pages: H449-H455
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Oxidative stress mediates tumor necrosis factor-α induced mitochondrial DNA damage and dysfunction in cardiac myocytes.2003
Author(s)
Suematsu N, Tsutsui H, Wen J, Kang D, Ikeuchi M, Ide T, Hayashidani S, Shiomi T, Kubota T, Hamasaki N, Takeshita A
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Journal Title
Circulation 107
Pages: 1418-1423
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Pioglitazone, peroxisome proliferator-activated receptor γ agonist, attenuates left ventricular remodeling and failure after experimental myocardial infarction2002
Author(s)
Shiomi T, Tsutsui H, Hayashidani S, Suematsu N, Ikeuchi M, Wen J, Ishibashi M, Kubota T, Egashira K, Takeshita A
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Journal Title
Circulation 106
Pages: 3126-3132
Description
「研究成果報告書概要(欧文)」より
