New molecular targeting therapy for regression of cardiac hypertrophy by inhibiting abnormal Ca2+ leak through RyR2 in hypertrophic cardiomyopathy

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670404
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Yamaguchi University
• Principal Investigator: YANO Masafumi 山口大学, 医学(系)研究科(研究院), 教授 (90294628)
• Co-Investigator(Kenkyū-buntansha): OKUDA Shinichi 山口大学, 大学院医学系研究科, 助教 (90530212)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 肥大型心筋症 / リアノジン受容体 / カルシウムリーク

Outline of Final Research Achievements

Hypertrophic cardiomyopathy(HCM) is a myocardial disorder characterized by idiopathic hypertrophy of the left ventricule. In familial HCM patients, it is the cause of sudden death by lethal arrhythmia in young age and the cause of heart failure disability at diastolic phase of HCM. However, medical approach of the regression of hypertrophy remains elusive. Here, we hypothesized that diastolic Ca2+ leak through ryanodine receptor (RyR2) is one of the important factor for triggering abnormal hypertrophy in HCM. To verify this hypothesis, we investigated the pathogenic role of Ca2+ leak through RyR2 in transgenic mouse (TG) model of familial HCM-related cardiac troponin T mutation. Diastolic Ca2+ leak through defective RyR2 caused by CaMKII activation was seen in TG cardiomyocytes and RyR2 stabilizer, dantrolene inhibited Ca2+ leak in TG. These results suggest that inhibiting Ca2+ leak by RyR2 stabilization might play a role for the regression of abnormal hypertrophy in HCM.

Free Research Field

循環器内科学