Development of new therapy for heart failure and arrhythmia by correction of signal transduction within cardiac ryanodine receptor

通过校正心脏兰尼碱受体内的信号转导开发心力衰竭和心律失常的新疗法

• 批准号: 20390226
• 负责人: YANO Masafumi
• 金额: $ 12.15万
• 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: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390226/
• 关键词: 筋小胞体; カルシウム; 心不全; 致死的不整脈; リアノジン受容体; 点突然変異

The defective inter-domain interaction between N-terminal and central domains within RyR2 reduces the binding affinity of CaM to RyR2, thereby causing the spontaneous Ca^<2+> release events in diseased hearts. Correction of the defective CaM binding may be a new strategy to protect against the aberrant Ca^<2+> release in heart failure and lethal arrhythmia.

RyR2的N端和中心结构域之间的结构域间相互作用缺陷降低了CaM与RyR2的结合亲和力，从而导致患病心脏中的自发性Ca^2+释放事件。纠正钙调素结合缺陷可能是一种新的策略，以防止异常的Ca^2+释放在心力衰竭和致命性心律失常。

项目成果

Increased Affinity of Calmodulin Binding to Cardiac Ryanodine Receptor Corrects the Defective Channel Gating in Failing Hearts

钙调蛋白与心脏兰尼定受体结合的亲和力增加可纠正衰竭心脏中的缺陷通道门控

• 发表时间: 2010
• 作者: Hino A;Yano M;Fukuda M;Suetomi T;Ono M;Xu X;Uchinoumi H;Susa T;Doi M;Okuda S;Kobayashi S;Yamamoto T;Matsuzaki M.
• 通讯作者: Matsuzaki M.

Polymorphic Ventricular Tachycardia Is Caused by Mutation-Linked Defective Conformational Regulation of the Ryanodine Receptor.

多形性室性心动过速是由与突变相关的瑞尼丁受体构象调节缺陷引起的。

• 发表时间: 2010
• 期刊: Circulation Research
• 影响因子: 20.1
• 作者: Okada S;Kozuka C;Masuzaki H;Yasue S;Ishii-Yonemoto T;Tanaka T;Yamamoto Y;Noguchi M;Kusakabe T;Tomita T;Fujikura J;Ebihara K;Hosoda K;Sakaue H;Kobori H;Ham M;Lee YS;Kim JB;Saito Y;Nakao K;中島淳;Hitoshi Uchinoumi
• 通讯作者: Hitoshi Uchinoumi

Defective Ca2+ cycling as a key pathogenic mechanism of heart failure.

Ca2 循环缺陷是心力衰竭的关键致病机制。

• 发表时间: 2008
• 期刊: Circ J. 72 Suppl A Review
• 作者: Yano M;Yamamoto T;Kobayashi S;Ikeda Y;Matsuzaki M.
• 通讯作者: Matsuzaki M.

Dissociation of calmodulin from cardiac ryanodine receptor causes aberrant Ca2+ release in heart failure

• DOI: 10.1093/cvr/cvq108
• 发表时间: 2010-09-01
• 期刊: CARDIOVASCULAR RESEARCH
• 影响因子: 10.8
• 作者: Ono, Makoto;Yano, Masafumi;Matsuzaki, Masunori
• 通讯作者: Matsuzaki, Masunori

Dantrolene, a Therapeutic Agent for Malignant Hyperthermia, Inhibits Catecholaminergic Polymorphic Ventricular Tachycardia in a RyR2R2474S/+ Knock-In Mouse Model

• DOI: 10.1253/circj.cj-10-0680
• 发表时间: 2010-12-01
• 期刊: CIRCULATION JOURNAL
• 影响因子: 3.3
• 作者: Kobayashi, Shigeki;Yano, Masafumi;Matsuzaki, Masunori
• 通讯作者: Matsuzaki, Masunori