Targetting ryanodine receptors for anti-heart failure and anti-arrhythmic therapy
Project/Area Number |
18K08039
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53020:Cardiology-related
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Research Institution | Yamaguchi University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
矢野 雅文 山口大学, 大学院医学系研究科, 教授 (90294628)
山本 健 山口大学, 大学院医学系研究科, 教授 (50363122)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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)
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Keywords | リアノジン受容体 / 心不全 / 致死的不整脈致死的不整脈 / ダントロレン / 心室頻拍 / カルシウムハンドリング / 悪性高熱症 / 不整脈 |
Outline of Final Research Achievements |
The purpose of this study is to develop a therapeutic method targeting RyR2 and apply it to clinical practice in patients with chronic heart failure and fatal arrhythmia. In a clinical study, a multicenter randomized double-blind study (SHO-IN Trial: UMIN 28766) was started to evaluate the prognosis and effect and safety of dantrolene on chronic heart failure and ventricular arrhythmia, and is currently underway. In basic research, we demonstrated the molecular mechanism of action and efficacy of RyR2 targeted therapy in vitro and in vivo using a mouse transverse coarctation (TAC) model and a mouse myocardial infarction (MI) model.
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Academic Significance and Societal Importance of the Research Achievements |
心臓型リアノジン受容体(RyR2)を標的としたダントロレンによる心不全・不整脈の新たな治療法がさまざまな基礎疾患を有する慢性心不全に対して有効かどうかを実証することを目的としている。ダントロレンのRyR2に対する新たな分子学的作用機序提唱から、動物実験レベルでダントロレンの抗心不全効果・抗不整脈効果を証明しており、極めて斬新かつ独創的である。ダントロレンは、悪性高熱症や全身こむら返り、痙性麻痺に保険適応が有り、薬物の安全性に関しては実証されているため、本研究で、有効性が実証されれば医療費の抑制にもつながり社会的貢献度は大である。また、RyR2を標的とした新たな創薬へと繋がっていくと考えられる。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Dantrolene prevents hepatic steatosis by reducing cytoplasmic Ca 2+ level and ER stress2020
Author(s)
Tamitani M, Yamamoto T, Yamamoto N, Fujisawa K, Tanaka S, Nakamura Y, Uchinoumi H, Oda T, Okuda S, Takami T, Kobayashi S, Sakaida I, Yano M.
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Journal Title
Biochem Biophys Rep.
Volume: 23:100787.
Pages: 100787-100793
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Localized Doxorubicin-Induced Cardiomyopathy Complicated With Shower Emboli Originating From Apical Intramural Thrombi2018
Author(s)
Ishiguchi H, Kobayashi S, Okuda S, Okamura T, Okada M, Takemura G, Takahashi M, Mikamo A, Hamano K, Yano M.
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Journal Title
Circulation Journal
Volume: 82
Issue: 9
Pages: 2375-2376
DOI
NAID
ISSN
1346-9843, 1347-4820
Year and Date
2018-08-24
Related Report
Peer Reviewed
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[Journal Article] Mutation-linked, excessively tight interaction between the calmodulin binding domain and the C-terminal domain of the cardiac ryanodine receptor as a novel cause of catecholaminergic polymorphic ventricular tachycardia.2018
Author(s)
Nishimura S, Yamamoto T, Nakamura Y, Kohno M, Hamada Y, Sufu Y, Fukui G, Nanno T, Ishiguchi H, Kato T, Xu X, Ono M, Oda T, Okuda S, Kobayashi S, Yano M.
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Journal Title
Heart Rhythm
Volume: 印刷中
Issue: 6
Pages: 905-914
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Anti-inflammatory approach for heart failure targeting Calcium-Calmodulin dependent protein kinase2020
Author(s)
Takeshi Suetomi, Michiaki Kono, Toshiro Kajii, Masaki Tamitani, Yoshihide Nakamura, Takayoshi Kato, Hitoshi Uchinoumi, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi, Takeshi Yamamoto, Masafumi Yano
Organizer
第84回日本循環器学会学術集会
Related Report
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