Development of comprehensive treatment of heart failure, hypertrophy, and arrhythmia by regulating intracellular Ca

调节细胞内Ca综合治疗心力衰竭、肥厚、心律失常的进展

• 批准号: 23390215
• 负责人: YANO Masafumi
• 金额: $ 12.31万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23390215/
• 关键词: 心不全; 筋小胞体; カルシウム; リアノジン受容体; EC-coupling; Ryanodine receptor; Calmodulin; CPVT

In this three years, we revealed that basic mechanism of arrhythmogenesity in CPVT and pressure overload HF is Ca leak from SR. The underlying mechanism of Ca leak is unzipping of channel reguratory domains and CaM binding domain. We also investigate the dantrolene, zipper of the channel reguratory domains and high affinity CaM as a therapeutic agents.

在这三年中，我们揭示了CPVT和压力超负荷HF中的代谢性肥胖的基本机制是SR的Ca泄漏，Ca泄漏的潜在机制是通道调节结构域和CaM结合结构域的解压缩。我们还研究了丹曲林、通道调节结构域的拉链和高亲和力钙调素作为治疗剂。

项目成果

Mutation-linked defective interdomain interactions within ryanodine receptor cause aberrant Ca²⁺release leading to catecholaminergic polymorphic ventricular tachycardia.

• DOI: 10.1161/circulationaha.111.023259
• 发表时间: 2011-08-09
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Suetomi T;Yano M;Uchinoumi H;Fukuda M;Hino A;Ono M;Xu X;Tateishi H;Okuda S;Doi M;Kobayashi S;Ikeda Y;Yamamoto T;Ikemoto N;Matsuzaki M
• 通讯作者: Matsuzaki M

New Data on Catecholaminergic Polymorphic Ventricular Tachycardia in Japan

日本儿茶酚胺能多形性室性心动过速的新数据

• DOI: 10.1253/circj.cj-13-0623
• 发表时间: 2013
• 期刊: Circulation Journal
• 影响因子: 3.3
• 作者: Shinichi Okuda;Masafumi Yano
• 通讯作者: Masafumi Yano

Novel Selective EP4 Receptor Agonists Restore the Intracellular Ca2+ Handling and the Cardiomyocyte Function in Heart Failure

新型选择性 EP4 受体激动剂可恢复心力衰竭时的细胞内 Ca2 处理和心肌细胞功能

• 发表时间: 2013
• 作者: Wakako Murakami;Shigeki Kobayashi;Takeki Myoren;Shigehiko Nishimura;Takayoshi Katoh;Masakazu Fukuda;Shinichi Okuda;Tetsuro Oda;Takeshi Yamamoto;Masafumi Yano
• 通讯作者: Masafumi Yano

Structure-Based Drug Design to Modulate RyR2 Function

基于结构的药物设计来调节 RyR2 功能

• 发表时间: 2011
• 作者: Shibata Y;et al.;Masafumi Yano
• 通讯作者: Masafumi Yano

Dantrolene May Suppress Arrhythmogenesis by Inhibition of CaMKII-mediated Aberrant Ca2+ Release Within the Ryanodine Receptor in Cardiac Troponin T-related Familial Hypertrophic Cardiomyopathy

丹曲林可能通过抑制心肌肌钙蛋白 T 相关家族性肥厚型心肌病的瑞尼定受体内 CaMKII 介导的异常 Ca2 释放来抑制心律失常发生

• 发表时间: 2013
• 作者: Shinichi Okuda;Masakazu Fukuda;Takayoshi Katoh;Shigehiko Nishimura;Shigeki Kobayashi;Takeshi Yamamoto;Masafumi Yano
• 通讯作者: Masafumi Yano