Novel therapeutic strategy against heart failure associated with cancer chemotherapy via the regulation of cardiac mitochondrial metabolism
| Project/Area Number |
17K08609
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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 |
General pharmacology
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| Research Institution | Tenri Health Care University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
的場 聖明 京都府立医科大学, 医学(系)研究科(研究院), 教授 (10305576)
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| Project Period (FY) |
2017-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | がん抑制遺伝子p53 / 心筋ミトコンドリア / 心不全 / 酸化ストレス / 遺伝子改変動物 / 心血管 / ミトコンドリア代謝 / 機能性食品成分 / 抗がん剤 / オートファジー / ミトコンドリア / 心筋代謝 / 心保護 |
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| Outline of Final Research Achievements |
We aimed to investigate the mechanisms underlying the progression of heart failure associated with cancer. For this purpose, we generated several genetically engineered mouse models and found that several metabolisms and their related molecules (TP53, D-glutamate, peroxisome proliferator-activated receptor-alpha, and D-β-hydroxybutyrate dehydrogenase 1) could be a potential therapeutic target of heart failure. The inhibition of the p53-TIGAR (TP53-Induced Glycolysis and Apoptosis Regulator) pathway reduced the oxidative stress and preserved the heart function in heart failure mice model. We also demonstrated that the p53 pathway was inhibited by bovine milk orotic acid, suggesting that this agent could be a novel promising drug for heart failure.
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| Academic Significance and Societal Importance of the Research Achievements |
医学研究の進歩によりがんは必ずしも不治の病ではなくなり、また社会の高齢化による心疾患の増加のため、がんと心疾患を合併する患者の増加が問題になっており、この数年の間に腫瘍循環器学という新しい学際分野も生まれてきた。本研究でがんと心臓の間の分子生物学的メカニズムの解明を進めたことは、この新しい学際分野にとって学術的意義がある。同時に、本研究で報告した治療介入に関する新しい知見は迅速な臨床展開につながり、社会的にも意義深いと考える。
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Report
(7 results)
Research Products
(29 results)
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[Journal Article] Measuring serum prothrombin in patients treated with warfarin or direct oral anticoagulants.2021
Author(s)
Kondo A, Kondo H, Nakagawa Y, Kameyama H, Ito H, Shimomura D, Yamanishi H, Hatanaka N, Yamamoto Y, Iwai-Kanai E, Matsuo S.
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Journal Title
Clin Chim Acta.
Volume: 524
Pages: 223-230
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] D-Glutamate is metabolized in the heart mitochondria.2016
Author(s)
M. Ariyoshi, M. Katane, K. Hamase, Y. Miyoshi, M. Nakane, A. Hoshino, Y. Okawa, Y. Mita, S. Kaimoto, M. Uchihashi, K. Fukai, K. Ono, S. Tateishi, D. Hato, R. Yamanaka, S. Honda, Y. Fushimura, E. Iwai-Kanai, N. Ishihara, M. Mita, H. Homma, and S. Matoba.
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Journal Title
Sci. Rep.
Volume: 7
Issue: 1
Pages: 43911-43911
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Cardiac TIGAR (TP53-induced glycolysis and apoptosis regulator) Reduces Myocardial Energetics and Cardiac Function in the Pressure Overload Heart Failure Model.2019
Author(s)
Yoshifumi Okawa, Atsushi Hoshino, Tomoya Kitani, Ryoetsu Yamanaka, Daichi Hato, Sakiko Honda, Yohei Fushimura, Ryota Urata, Yoshito Minami, Shyo Hashimoto, Ayumi Matsuki, Shunta Taminishi, Toshiyuki Nishiji, Tomohiro Hino, Nobuichiro Yagi, Eri Iwai-Kanai, Satoaki Matoba
Organizer
BCVS Scientific Sessions 2019
Related Report
Int'l Joint Research
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