| Project/Area Number |
26461123
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Gunma University |
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Principal Investigator |
Iso Tatsuya 群馬大学, 大学院医学系研究科, 准教授 (10400756)
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| Co-Investigator(Kenkyū-buntansha) |
倉林 正彦 群馬大学, 大学院医学系研究科, 教授 (00215047)
菱木 貴子 慶應義塾大学, 医学部(信濃町), 講師 (10338022)
小板橋 紀通 群馬大学, 医学部附属病院, 助教 (10420093)
山本 正道 京都大学, 医学研究科, 特任講師 (70423150)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 分子心臓病 / エネルギー代謝 / 脂肪酸 / グルコース / 心不全 / 構造リモデリング / 代謝リモデリング / 毛細血管 / 内皮細胞 |
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| Outline of Final Research Achievements |
Under increased workload, the heart shows structural (cardiac hypertrophy and fibrosis) and metabolic remodeling. Double knockout mice lacking FABP-4 and -5 and CD36 knockout mice exhibit reduced uptake of fatty acid with a robust increase in glucose uptake by metabolic compensation. When hearts were pressure-overloaded by trans-aortic constriction, cardiac contractile dysfunction was markedly exacerbated in both mice. Metabolic analysis revealed that pool size of the TCA cycle, or total energy supply, was significantly reduced despite a further increase in glucose uptake by TAC, leading to a reduction in ATP synthesis. In contrast, de novo synthesis of molecules for cardiac hypertrophy (i.e. amino acids, nucleic acids and fatty acids) was likely to be facilitated despite a reduction in total energy supply. Thus, the heart favors anabolic reactions rather than ATP synthesis during the development of cardiac hypertrophy even under conditions where total energy supply is limited.
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