| Project/Area Number |
17K11604
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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 |
Emergency medicine
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Akiyama Tsuyoshi 国立研究開発法人国立循環器病研究センター, 研究所, 客員研究員 (70202554)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 心虚血・再灌流 / セロトニン / 血小板 / トランスポーター / 心筋細胞傷害 / マイクロダイアリシス法 / 心虚血▪再灌流 / セロトニン（５－ＨＴ） |
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| Outline of Final Research Achievements |
Serotonin (5-HT) accumulates in the heart during myocardial ischemia and induces deleterious effects on the cardiomyocytes through receptor-dependent and monoamine oxidase-dependent pathways. During myocardial ischemia, depletion of ATP inhibits both sodium-potassium ATPase of cell membrane and ATP dependent vesicle transport of vesicle membrane and causes carrier-mediated 5-HT efflux from platelet via reverse-mode of 5-HT reuptake transporter, which is sensitive to the selective 5-HT reuptake inhibitor. During myocardial reperfusion, accumulated interstitial 5-HT is taken up into cardiac cells via plasma membrane monoamine transporter, one of extra-neuronal monoamine transporters and then metabolized by monoamine oxidase to produce 5-hydroxyindole acetic acid and hydrogen peroxide, which causes myocardial cell injury.
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| Academic Significance and Societal Importance of the Research Achievements |
急性心筋梗塞症の急性期治療において、心筋細胞傷害を減弱させることは、その後の心不全への移行を防ぎ、予後を改善させることが可能であるが、いまだにその有効な治療法は見つかっていない。我々の心虚血・再灌流時における虚血部セロトニン動態の研究成果から、虚血時のセロトニン放出、および再灌流時におけるセロトニン代謝を抑制して、心筋細胞傷害を減弱させることが可能であり、急性心筋梗塞症急性期の新たな治療法につながると考えられる。
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