| Project/Area Number |
22659154
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Yamaguchi University |
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Principal Investigator |
YANO Masafumi 山口大学, 医学部附属病院, 講師 (90294628)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Takeshi 山口大学, 大学院・医学系研究科, 助教 (50363122)
IKEDA Yasuhiro 山口大学, 大学院・医学系研究科, 助教 (00260349)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,160,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,600,000 (Direct Cost: ¥1,600,000)
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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 / カルシウム動態 / 筋小胞体 / カルシウム / 心不全 / 致死的不整脈 / 点突然変異 |
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| Research Abstract |
Hypertrophic cardiomyopathy(HCM) is known to be a myocardial disorder characterized by idiopathic hypertrophy of the left ventricule. In HCM patients, sudden death occurs owing to lethal arrhythmia in young age and diastolic heart failure can be sometimes developed. Medical approach for regression of hypertrophy in HCM patients remains elusive. Here, we hypothesized that diastolic Ca2+ leak through ryanodine receptor(RyR2) might predispose to abnormal hypertrophy in HCM patients. 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, which was found to stabilize RyR2 inhibited Ca2+ leak. These results suggest that stabilization of RyR2 and subsequent inhibition of Ca2+ leak might play a pivotalrole for regression of abnormal hypertrophy in HCM patients.
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