| Project/Area Number |
23790856
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Yamaguchi University |
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Principal Investigator |
OKUDA Shinichi 山口大学, 医学部附属病院, 助教 (90530212)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 肥大型心筋症 / カルシウムハンドリング / リアノジン受容体 / ドメイン連関 / 致死性不整脈 |
|---|
| Research Abstract |
Hypertrophic cardiomyopathy(HCM) is known to be a myocardial disorder characterized by severe hypertrophy of the left ventricule. In HCM patients, it is the cause of sudden death by lethal arrhythmia in younger age. Medical approach against inductive ventricular arrhythmia in HCM patients remains elusive. Here, we hypothesized that diastolic Ca2+ leak through Ryanodine receptor (RyR2) is one of the important factor of regulating arrhytmogenesis in HCM. To verify this hypothesis, we investigated the pathogenic role of Ca2+ leak through RyR2 in transgenic mouse (TG) model of Familial Hypertrophic cardiomyopathy-related cardiac troponin T mutation. Diastolic Ca2+ leak through defective RyR2 is induced by beta-adrenergic stimulation in TG cardiomyocytes. Dantrolene and Calmodulin-kinaseII inhibitor can inhibit Ca2+ leak by stabilizing RyR2. These results might suggest that the stabilization of RyR2 and inhibiting Ca2+ leak might play a role for the pathogenesis of lethal arrhythmia in HCM.
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