Molecular mechanism of contractile dysfunction and the alteration of intracellular Ca^<2+> handling caused by mutation of cardiac troponin T

心肌肌钙蛋白T突变引起收缩功能障碍及细胞内Ca^2处理改变的分子机制

• 批准号: 19500357
• 负责人: KURIHARA Satoshi
• 金额: $ 2.75万
• 依托单位: Jikei University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19500357/
• 关键词: 心筋; トロポニンT; Ca^<2+>感受性; アンギオテンシンII受容体; Ca^<2+>; トロポニン; 細胞内Ca^<2+>; 筋小胞体; Ca感受性; 拡張型心筋症; Caトランジェント; アンギオテンシンII; DCM; マウス; 細胞内Ca; Ca transient; レニン・アンギオテンシン系; 心エコー; Ca 感受性; 細胞内Ca2^<2+>; CaMKII

We explored the mechanism of pathogenesis and sudden death in dilated cardiomyopathy using knock-in mouse model with mutant troponin T (DCM mouse). DCM mouse died suddenly from age of 1 month old. In DCM mouse, cardiac chamber was dilated and contractile functions were impaired. A blocker of angiotensin II receptor (ARB) significantly increased survival rate and improved the cardiac functions without changing the decreased Ca^<2+> sensitivity in DCM mouse. ARB also improved the fibrosis and electrocardiogram, which were considered as critical for the beneficial effects of ARB.

我们使用突变的肌钙蛋白T（DCM小鼠）敲打小鼠模型探索了发病机理和猝死的机制。 DCM老鼠从1个月大的时候突然死亡。在DCM小鼠中，心脏腔室扩张，收缩功能受损。血管紧张素II受体（ARB）的阻滞剂可显着提高存活率并改善心脏功能，而不会改变DCM小鼠中Ca^<2+>敏感性的降低。 ARB还改善了纤维化和心电图，这被认为对ARB的有益作用至关重要。

项目成果

Rennin-angiotensin system plays an important role in the pathogenesis of DCM in mouse.

肾素-血管紧张素系统在小鼠扩张型心肌病的发病机制中发挥着重要作用。

• 发表时间: 2009
• 作者: Hongo K;Morimoto S;O-uchi J;Kusakari Y;Komukai K;Kawai M;Yoshimura M;Morimoto S;Ohtsuki I;Takeda N;Kurihara S
• 通讯作者: Kurihara S

Thin filament-based regulation of length-dependent activation in skinned porcine ventricular muscle

基于细丝的去皮猪心室肌长度依赖性激活的调节

• 发表时间: 2009
• 作者: Terui T;Shimamoto Y;Sodnomtseren M;Yamane M;Ohtsuki I;Ishiwata S;Kurihara S;Fukuda N
• 通讯作者: Fukuda N

Renin-angiotensin system plays an important role in the pathogenesis of DCM in mouse

肾素-血管紧张素系统在小鼠DCM发病机制中发挥重要作用

• 发表时间: 2009
• 作者: 本郷賢一;吉村道博;Hongo K
• 通讯作者: Hongo K

Physiological functions of the giant elastic protein titin in mammalian striated muscle

• DOI: 10.2170/physiolsci.rv005408
• 发表时间: 2008-06-01
• 期刊: JOURNAL OF PHYSIOLOGICAL SCIENCES
• 影响因子: 2.3
• 作者: Fukuda, Norio;Granzier, Henk L.;Kurihara, Satoshi
• 通讯作者: Kurihara, Satoshi

Molecular basis for the Frank-Starling mechanism of the heart.

心脏弗兰克-斯塔林机制的分子基础。

• 发表时间: 2008
• 作者: Kurihara S;Fukuda N;Ohtsuki I;Terui T;Hongo K;Komukai K;Ishikawa T
• 通讯作者: Ishikawa T