Investigation of novel heart failure therapy targeting transcription complex
| Project/Area Number |
17K08279
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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 |
Biological pharmacy
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| Research Institution | University of Shizuoka |
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Principal Investigator |
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 心筋細胞肥大 / 心不全 / p300 / エピジェネティック / ヒストン / ヒストンアセチルトランスフェラーゼ / ドラッグリポジショニング / ω３系脂肪酸 / 転写因子 / GATA4 / 治療薬 / ヒストンアセチル化酵素 |
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| Outline of Final Research Achievements |
We examined the in vitro screening system using natural product compound libraries and known drug libraries and found compounds that strongly suppress the HAT activity of p300, which is a therapeutic target for heart failure. Next, we performed whether these candidate compounds for the treatment of heart failure could inhibit the cardiomyocyte hypertrophy in cultured neonatal rat cardiomyocytes. We identified some of these compounds that possessed the more strongly and more myocardial-specific hypertrophic inhibitory effect at low concentrations. Furthermore, we found that ω3 fatty acids suppressed the progression of heart failure in myocardial infarction rat model.
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| Academic Significance and Societal Importance of the Research Achievements |
心不全は高血圧性心疾患、弁膜症、虚血性心疾患など種々の心疾患の共通最終像であり、この問題を解決することは極めて重要である。現在に薬物治療を用いても心不全の生命予後は悪く、あらたな心不全治療薬の開発が必要である。我々は、ω３系脂肪酸が動物モデルの心不全の進行を抑制することを見出した。すでに臨床で用いられる薬物を心不全治療に応用できれば、開発期間や費用も削減できるだけでなく、新たな心不全治療法の開発に貢献することが期待される。
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Report
(4 results)
Research Products
(72 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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[Journal Article] Role of SIRT1 in Modulating Acetylation of the Sarco-Endoplasmic Reticulum Ca2+-ATPase in Heart Failure.2019
Author(s)
Gorski PA, Jang SP, Jeong D, Lee A, Lee P, Oh JG, Chepurko V, Yang DK, Kwak TH, Eom SH, Park ZY, Yoo YJ, Kim DH, Kook H, Sunagawa Y, Morimoto T, Hasegawa K, Sadoshima J, Hajjar RJ, Park WJ, Kho C.
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Journal Title
Circ Res.
Volume: 124(9)
Issue: 9
Pages: 63-80
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Natural products derived from Jamu, prevent the development f cardiomyocyte hypertrophy and fibrosis phenotype in primary cultured cells2019
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4回J-ISCP年次学術集会
Related Report
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[Presentation] An Anti-Hypertrophic Effect On An Active Edible Ginger Components, Zerumbone In Heart Failure Model Mice2019
Author(s)
Nurmila Sari, Yasufumi Katanasaka, Hikaru Sato, Yuga Sugiyama, Yusuke Miyazaki, Yoichi Sunagawa, Masafumi Funamoto, Kana Shimizu, Satoshi Shimizu, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
Organizer
Bandung International Conference on Food and Health
Related Report
Int'l Joint Research
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[Presentation] Zerumbone Inhibits Cardiac Remodering and Dysfunction in Pressure Overload-induced Heart Failure Model Mice2019
Author(s)
Yuga Sugiyama, Nurmila Sari, Yasufumi Katanasaka, Yoichi Sunagawa, Yusuke Miyazaki, Masafumi Funamoto, Satoshi Shimizu, Kana Shimizu, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
Organizer
第24回静岡健康・長寿フォーラム
Related Report
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[Presentation] The effect of natural extracts on cardiomyocyte hypertrophy2019
Author(s)
Tatsuya Makawa, yoichi Sunagawa, Masafumi Funamoto, Yasufumi Katanasaka, Yusuke Miyazaki, Kana Shimizu, Nurmila Sari, Satoshi Shimizu, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
Organizer
第24回静岡健康・長寿フォーラム
Related Report
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[Presentation] Omega-3 fatty acids, EPA and DHA, Repress p300-HAT-induced Hypertrophic Responses and Prevent MI-induced Development of Heart Failure2019
Author(s)
Ayumi Katayama, Yoichi Sunagawa, Masafumi Funamoto, Kana Shimizu, Mai Genpei, Yusuke Miyazaki, Yasufumi Katanasaka, Nurmila Sari, Satshi Shimizu, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
Organizer
第24回静岡健康・長寿フォーラム
Related Report
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[Presentation] Effects of Jamu component on cardiomyocyte hypertrophy and fibrotic pheotype in primary cultured cells2019
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24回静岡健康・長寿フォーラム
Related Report
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[Presentation] The 5-HT2A Receptor Antagonist Sarpogrelate Suppresses Pressure Overload-Induced Development of Heart Failure in Mice2019
Author(s)
Kana Shimizu, Masafumi Funamoto, Yoichi Sunagawa, Yasufumi Katanasaka, Yusuke Miyazaki, Noriyuki Murai, Hiroki Honda, Satoshi Shimizu, Nurmila Sari, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
Organizer
AHA 2019
Related Report
Int'l Joint Research
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