Molecular mechanisms of an improvement in prognosis in the mouse model of dilated cardiomyopathy treated by inhibition of the RAA system

抑制 RAA 系统治疗扩张型心肌病小鼠模型预后改善的分子机制

• 批准号: 22300130
• 负责人: KURIHARA Satoshi
• 金额: $ 5.74万
• 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 (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22300130/
• 关键词: 細胞内Ca^<2+>; トロポニン; Ca^<2+>感受性; アンギオテンシン; 拡張型心筋症; 細胞内Ca; 線維化; RAA系; Ca感受性

We investigated the role of the renin-angiotensin-aldosterone system (RAA system) on the dilated cardiomyopathy, to clarify the molecular mechanism and morphological changes in heart failure.By inhibition of the RAA system, survival rate of the mouse model of dilated cardiomyopathy was significantly improved. We conclude that the possible mechanisms of RAA inhibition for improving life-span of dilated cardiomyopathy should include (1) inhibition of fibrosis and (2) an enhancement of contractility without improvement of the Ca_ sensitivity.

本研究探讨了肾素-血管紧张素-醛固酮系统（RAA系统）在扩张型心肌病发病中的作用，阐明其在心力衰竭中的分子机制和形态学改变，通过抑制RAA系统，可显著提高扩张型心肌病小鼠模型的存活率。结论：抑制RAA延长扩张型心肌病患者生存期的可能机制包括：（1）抑制纤维化;（2）增强心肌收缩力，但不改善Ca敏感性。

项目成果

Selective Modulation of SERCA Did Not Affect Ca2+ Leak from Sarcoplasmic Reticulum in Transgenic Mouse Models.

SERCA 的选择性调节不影响转基因小鼠模型中肌浆网的 Ca2 泄漏。

• 作者: Ogata;S.;Miki;T.;Seino;S.;Tamai;S.;Kasai;H. & Nemoto;T.;Morimoto S
• 通讯作者: Morimoto S

心筋線維化における興奮収縮連関

心肌纤维化中的兴奋-收缩耦合

• 发表时间: 2012
• 作者: Miyashita T;Hatsuta H;Murayama S;Saito Y;Tuskie T;Ihara Y;Kuwano R;草刈洋一郎,浦島崇,栗原敏
• 通讯作者: 草刈洋一郎,浦島崇,栗原敏

Compensatory Increase in the Ca2+ Transient Is Important for Contractile Recovery of Dilated Cardiomyopathy in Mice.

Ca2 瞬变的代偿性增加对于小鼠扩张型心肌病的收缩恢复很重要。

• 作者: Shigeno K;Ogita H;Funabiki K;Hongo K
• 通讯作者: Hongo K

Impairment of E-C coupling in cardiac papillary muscle with fibrosis induced by pressure overload

压力超负荷引起的心肌乳头肌 E-C 耦合损伤及纤维化

• 发表时间: 2012
• 作者: Kusakari Y;Urashima T;Kurihara S
• 通讯作者: Kurihara S

Properties of sarcomeric self-oscillations in rat neonatal cardiomyocytes: Relationship with heart beats by responce of electrical stimuli

大鼠新生心肌细胞肌节自振荡的特性：电刺激反应与心跳的关系

• 发表时间: 2012
• 作者: Shintani S;Yamane M;Oyama K;Kurihara S;Ishiwata S;Fukuda N
• 通讯作者: Fukuda N