| Project/Area Number |
18K08121
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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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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Department of Clinical Research, National Hospital Organization Kyoto Medical Center |
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Principal Investigator |
Hasegawa Koji 独立行政法人国立病院機構(京都医療センター臨床研究センター), 展開医療研究部, 研究部長 (50283594)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 心筋細胞 / 情報伝達 / 薬物療法 / 転写調節因子 / 心不全 / 循環器・高血圧 / シグナル伝達 / 薬学 / トランスレーショナルリサーチ / トランスレーショナルリサ ーチ |
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| Outline of Final Research Achievements |
We have playing a pioneering role in elucidating signal transduction mechanisms in cardiomyocyte nuclei in the development of heart failure, aiming at establishing novel heart failure therapy targeting cardiomyocyte nuclei. In addition, we have conducted research in order to enhance the activity of curcumin, which possesses histone acetylation enzyme inhibitory activity. In an animal model, we found that the acetylation domain site of histone changed from cardiac hypertrophy to heart failure stage. We also found a compound that suppresses histone acetylation activity in cardiac myocytes at low concentrations. These findings are very important for the establishment of fundamental heart failure pharmacotherapy that targets the final common pathway of intracellular signal transduction.
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| Academic Significance and Societal Importance of the Research Achievements |
高血圧による圧負荷、心筋梗塞による細胞死などのストレスが心臓に加わると、そのシグナルは様々な神経・体液性因子に変換される。これらが心不全の発症ならびに増悪に関与しており、β-交感神経遮断薬やアンジオテンシン拮抗薬が心不全の治療の基本として確立されたが、その後の薬物療法には著明な進展が見られてない。無数の細胞外液性因子を標的とするよりも、細胞内情報伝達の最終共通経路を標的とした、より根本的な心不全発症・増悪抑制の薬物療法の確立が、21世紀の高齢化社会において是非必要である。
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