Comprehensive treatment of heart failure, cardiac hypertrophy, and arrhythmia by controlling ryanodine receptor bound calmodulin
Project/Area Number |
17H04178
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cardiovascular medicine
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Research Institution | Yamaguchi University |
Principal Investigator |
YANO Masafumi 山口大学, 大学院医学系研究科, 教授 (90294628)
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Co-Investigator(Kenkyū-buntansha) |
小田 哲郎 山口大学, 医学部附属病院, 助教 (40569290)
山本 健 山口大学, 大学院医学系研究科, 教授 (50363122)
小林 茂樹 山口大学, 大学院医学系研究科, 准教授 (90397993)
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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 |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | リアノジン受容体 / カルモジュリン / 心肥大 / 心不全 / 不整脈 / EC coupling |
Outline of Final Research Achievements |
We have succeeded in creating mice genetically invcreasing the affinity of calmodulin to ryanodine receptor. This mouse was able to suppress arrhythmia completely by mating with CPVT type KI mouse. There was almost no death from heart failure after TAC surgery, and cardiac hypertrophy did not occur while maintaining cardiac function. In clinical studies, the multicenter, double-blind, randomized SHO-IN trial demonstrating the efficacy of dantrolene for heart failure and severe arrhythmias currently has more than 150 enrolled cases.
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Academic Significance and Societal Importance of the Research Achievements |
重症心不全における致死的不整脈を抑制するこれまでとは全く異なる方法を解明した。心肥大について、その機序にリアノジン受容体結合カルモジュリンの核内移行があるという全く新しい肥大の機序を明らかにした。さらに心肥大はなくても心機能は保たれ、よい代償性肥大などというものはないことを示した。
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Report
(4 results)
Research Products
(22 results)
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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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[Journal Article] Correction of impaired calmodulin binding to RyR2 as a novel therapy for lethal arrhythmia in the pressure-overloaded heart failure.2017
Author(s)
Kato T, Yamamoto T, Nakamura Y, Nanno T, Fukui G, Sufu Y, Hamada Y, Maeda T, Nishimura S, Ishiguchi H, Murakami W, Fukuda M, Xu X, Hino A, Ono M, Oda T, Okuda S, Kobayashi S, Koseki N, Kyushiki H, Yano M.
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Journal Title
Heart Rhythm
Volume: 14
Issue: 1
Pages: 120-127
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Urinary 8-Hydroxy-2′-Deoxyguanosine as a Myocardial Oxidative Stress Marker Is Associated With Ventricular Tachycardia in Patients With Active Cardiac Sarcoidosis2017
Author(s)
Ishiguchi H, Kobayashi S, Myoren T, Kohno M, Nanno T, Murakami W, Oda S, Oishi K, Okuda S, Okada M, Suga K, Yano M.
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Journal Title
Cardiovascular Imaging,
Volume: 10
Issue: 12
DOI
Related Report
Peer Reviewed
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[Journal Article] Serial changes in the side-branch ostial area after main-vessel stenting with kissing balloon inflation for coronary bifurcation lesions, assessed by 3D optical coherence tomography.2017
Author(s)
Fujimura T, Okamura T, Tateishi H, Nakamura T, Yamada J, Oda T, Mochizuki M, Nishimura S, Nishimura T, Yano M.
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Journal Title
Eur Heart J Cardiovasc Imaging
Volume: -
Issue: 10
Pages: 1-9
DOI
Related Report
Peer Reviewed
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[Presentation] The Difference of Calmodulin-Ryanodine Receptor Affinity Between N-terminal, Central and C-terminal RyR2-CPVT Knock-in Mice2019
Author(s)
Hitoshi Uchinoumi, Xiaoqiong Dong, Ivanita Stefanon, Mena Said, Rogerio Faustino, Razvan L Cornea, Univ of Minnesota, Xander H.t. Wehrens, Takeshi Yamamoto, Masafumi Yano, Donald M Bers
Organizer
AHA Scientific Sessions 2019
Related Report
Int'l Joint Research
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[Presentation] Critical Role of Ryanodine Receptor Bound Calmodulin to Prevent Catecholaminergic Polymorphic Ventricular Tachycardia2019
Author(s)
Yoshihide Nakamura, Takeshi Yamamoto, Shigeki Kobayashi, Masaki Tamitani, Yoriomi Hamada, Go Fukui, Xiaojuan Xu, Shigehiko Nishimura, Takayoshi Kato, Hitoshi Uchinoumi, Tetsuro Oda, Shinichi Okuda, Masafumi Yano
Organizer
AHA BCVS
Related Report
Int'l Joint Research
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[Presentation] Channel Pore Mutation of RyR2 Cause Calcium Leak Independent of FKBP12.6-RyR2 and Calmodulin-RyR2 Affinity in R4496C/+ Knock-in Mouse2017
Author(s)
Hitoshi Uchinoumi, Ivanita Stefanon, Yi Yang, Mena Said, Xiaoqiong Dong, Rogerio Faustino, Jose L Puglisi, Ye Chen-Izu, Razvan L Cornea, Xander H Wehrens, Wayne S Chen, Takeshi Yamamoto, Yano Masafumi and Donald M Bers
Organizer
90th Scientific Session of American Heart Association
Related Report
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[Presentation] Effect of Site Dependent RyR Stabilizers; a Clue to Trace a Signal Transmission Pathway Inside the RyR Molecule2017
Author(s)
Go Fukui, Takeshi Yamamoto, Michiaki Kono, Yoshihide Nakamura, Takuma Nanno, Yoriomi Hamada, Yoko Sufu, Hironori Ishiguchi, Shigehiko Nishimura, Hitoshi Uchinoumi, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi and Masafumi Yano
Organizer
90th Scientific Session of American Heart Association
Related Report
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[Presentation] Dantrolene Prevents Right Ventricular Hypertrophy Without Reducing Pulmonary Arterial Pressure In Monocrotaline-induced PAH In Mice2017
Author(s)
Yoshihide Nakamura, Takeshi Yamamoto, Michiaki kono, Yoriomi Hamada, Go Fukui, Yoko Sufu, Takuma Nanno, Hironori Ishiguchi, Shigehiko Nishimura, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi, Masafumi Yano
Organizer
90th Scientific Session of American Heart Association
Related Report