Translational research for the development of novel heart failure therapy that targets signaling pathway in cardiac myocytes
| 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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Report
(4 results)
Research Products
(26 results)
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[Journal Article] The Synthetic Curcumin Analogue GO-Y030 Effectively Suppresses the Development of Pressure Overload-induced Heart Failure in Mice.2020
Author(s)
Shimizu K, Sunagawa Y, Funamoto M, Wakabayashi H, Genpei M, Miyazaki Y, Katanasaka Y, Sari N, Shimizu S, Katayama A, Shibata H, Iwabuchi Y, Kakeya H, Wada H, Hasegawa K, Morimoto T.
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Journal Title
Sci Rep.
Volume: 10(1)
Issue: 1
Pages: 7172-7172
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] Sarpogrelate, a Selective Serotonin2aReceptor Antagonist, Suppresses Pressure Overlaod-induced Cardiac Hypertrophy and Systolic Dysfunction Through Inhibiting Erk1/2/gata4 Pathway2020
Author(s)
Kana Shimizu, Masafumi Funamoto, Yoichi Sunagawa, Yasufumi Katanasaka, Yusuke Miyazaki, Noriyuki Murai, Hiroki Honda, Yoshiki Kawakami, Satoshi Shimizu, Nurmila Sari, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
Organizer
American Heart Association Scientific Sessions 2020
Related Report
Int'l Joint Research
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[Presentation] Epa and Dha Suppressed Myocardial Infarction-induced Systolic Dysfunction by Inhibiting P300 Hat Activity2020
Author(s)
Masafumi Funamoto, Yoichi Sunagawa, Yasufumi Katanasaka, Kana Shimizu, Yusuke Miyazaki, Nurmila Sari, Satoshi Shimizu, Kiyoshi Mori, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
Organizer
American Heart Association Scientific Sessions 2020
Related Report
Int'l Joint Research
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[Presentation] Identification of Active Compound from Indonesia Traditional Medicine for Heart Failure Prevention2020
Author(s)
Nurmila Sari, Yasufumi Katanasaka, Yuga Sugiyama, Yusuke Miyazaki, Yoichi Sunagawa, Masafumi Funamoto, Satoshi Shimizu, Kana Shimizu, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto.
Organizer
第84回日本循環器学会学術集会
Related Report
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[Presentation] Identification of Anti-hypertrophic Compounds from Natural Compounds2020
Author(s)
前川 健也 , 砂川 陽一, 船本 雅文, 刀坂 泰史, 宮崎雄輔, 清水 果奈, Sari Nurmila, 清水 聡史, 和田啓道, 長谷川 浩二, 森本 達也.
Organizer
第84回日本循環器学会学術集会
Related Report
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