2007 Fiscal Year Final Research Report Summary
Analysis of the role of mitochondrial transcription factor in cardiovascular diseases and the development of novel therapeutic strategies
| 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)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Mitochondria / Transcription factor / Genes / Mitochondrial DNA / Oxidative stress / Cardiovascular diseases / Hypertension / Heart failure |
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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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Research Products
(132 results)
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[Journal Article] Allograft inflammatory factor-1 augments macrophage phagocytotic activity and accelerates the progression of atherosclerosis in ApoE-/- mice.2008
Author(s)
Mishima T, Iwabuchi K, Fujii S, Tanaka S, Ogura H, Watano-Miyata K, Ishimori N, Andoh Y, Nakai Y, Iwabuchi C, Ato M, Kitabatake A, Tsutsui H, Onoe K
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Journal Title
Int J Mol Med 21(2)
Pages: 181-187
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Prevalence and clinical importance of spontaneous echo contrast within the carotid artery in patients with ischemic cerebrovascular disease.2007
Author(s)
Onozuka H, Muraki M, Mikami T, Yoshimoto T, Yoshizumi T, Kitaguchi M, Sugawara T, Tokuda K, Kaneko S, Kashiwaba T, Yamada S, Tsutsui H, Kitabatake A
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Journal Title
J Ultrasound Med 26
Pages: 169-77
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Overexpression of mitochondrial peroxiredoxin-3 prevents left ventricular remodeling and failure after myocardial infarction in mice.2006
Author(s)
Matsushima S, Ide T, Yamato M, Matsusaka H, Hattori F, Ikeuchi M, Kubota T, Sunagawa K, Hasegawa Y, Kurihara T, Oikawa S, Kinugawa S, Tsutsui H
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Journal Title
Circulation 113
Pages: 1779-1786
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A fundamental study for quantitative measurement of ultrasound contrast concentration by low mechanical index contrast ultrasonography.2006
Author(s)
Yamada S, Komuro K, Taniguchi M, Uranishi A, Komatsu H, Asanuma T, Ishikura F, Onozuka H, Mikami T, Tsutsui H, Beppu S
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Journal Title
J Med Ultrasonics 33
Pages: 77-83
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Lower prevalence of circulating natural killer T cells in patients with angina: a potential novel marker for coronary artery disease.2006
Author(s)
Andoh Y, Fujii S, Iwabuchi K, Yokota T, Inoue N, Nakai Y, Mishima T, Yamashita T, Nakagawa T, Kitabatake A, Onoe K, Tsutsui H
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Journal Title
Coronary Artery Dis 17
Pages: 523-528
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Chronic β-Adrenergic receptor stimulation enhances the expression of G-Protein coupled receptor kinases, GRK2 and GRK5, in both the heart and peripheral lymphocytes.2005
Author(s)
Oyama N, Urasawa K, Kaneta S, Sakai H, Saito T, Takagi C, Yoshida I, Kitabatake A, Tsutsui H
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Overexpression of mitochondrial transcription factor a ameliorates mitochondrial deficiencies and cardiac failure after myocardial infarction.2005
Author(s)
Ikeuchi M, Matsusaka H, Kang D, Matsushima S, Ide T, Kubota T, Fujiwara T, Hamasaki N, Takeshita A, Sunagawa K, Tsutsui H
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Journal Title
Circulation 112
Pages: 683-690
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Usefulness of left parasternal approach for the continuous-wave doppler measurement of left ventricular outflow tract pressure gradient in patients with hypertrophic cardiomyopathy.2005
Author(s)
Onozuka H, Mikami T, Kaga S, Yamada S, Nishihara K, Komuro K, Inoue M, Teranishi J, Urasawa K, Tsutsui H, Kitabatake A
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Journal Title
J of Echocardiography 3
Pages: 140-147
Description
「研究成果報告書概要(欧文)」より
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