| Project/Area Number |
18K08108
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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 | Yamaguchi University |
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Principal Investigator |
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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)
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) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | リアノジン受容体 / カルモジュリン / 心肥大 / 不整脈 / 心不全 / 致死的不整脈 |
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| Outline of Final Research Achievements |
The principal investigator discovered an amino acid mutation that significantly enhances the binding affinity of CaM for RyR2, and succeeded in creating a knock-in (KI) mouse: (RyR2 V3599K KI mouse) incorporating this mutation. By mating these mice with R2474S CPVT type mice, CaM dissociation during catecholamine stimulation was suppressed, and the motor-induced ventricular tachycardia that occurs in CPVT mice completely disappeared. In this RyR2 V3599K KI mouse, cardiac enlargement and cardiac hypertrophy due to TAC were almost completely suppressed. Furthermore, in WT mice, CaM was dissociated from RyR2 after 2 weeks of TAC, whereas it was suppressed in KI mice.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、新しい心不全、心肥大の治療法をもたらす。左心不全のみならず、肺高血圧に伴う右心不全にも応用できると考える。また、SRからのCa2+ leak抑制のみならず、心筋以外の組織ではERからのCa2+ leak抑制によりER stressを抑制できるため、アルツハイマー病、糖尿病、脂肪肝炎など様々な疾患への応用が可能となる可能性がある。
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