Cardiac functional improvement in rats with myocardial infarction by up-regulating cardiac myosin light chain kinase with neuregulin

被引：57

作者：

Gu, Xinghua ^{[1
,2
]}

Liu, Xifu ^{[2
]}

Xu, Danling ^{[1
]}

Li, Xinyan ^{[2
]}

Yan, Ming ^{[2
]}

Qi, Ying ^{[2
]}

Yan, Weihai ^{[2
]}

Wang, Wenqing ^{[2
]}

Pan, Jing ^{[2
]}

Xu, Yabei ^{[2
]}

Xi, Bing ^{[2
]}

Cheng, Leilei ^{[1
]}

Jia, Jianguo ^{[1
]}

Wang, Keqiang ^{[1
]}

Ge, Junbo ^{[1
]}

Zhou, Mingdong ^{[2
]}

机构：

[1] Fudan Univ, Zhongshan Hosp, Shanghai Inst Cardiovasc Dis, Shanghai 200032, Peoples R China

[2] Zensun Shanghai Sci & Tech Ltd, Shanghai 201203, Peoples R China

来源：

CARDIOVASCULAR RESEARCH | 2010年 / 88卷 / 02期

关键词：

Recombinant human neuregulin-1; Cardiac myosin light chain kinase; Myosin light chain 2 ventricular; RNA interference; Transgene; GENE-EXPRESSION; PHOSPHORYLATION; APOPTOSIS; CONTRACTILITY; SURVIVAL; PROTEIN; CELLS; HEART; SIZE;

D O I：

10.1093/cvr/cvq223

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Recombinant human neuregulin-1 (rhNRG-1) improves cardiac function in experimental heart failure models, but the underlying mechanism remains largely unknown. In this study, we evaluated whether rhNRG-1 could improve cardiac function via the cardiac myosin light chain kinase/myosin light chain 2 ventricular (cMLCK/MLC-2v) pathway in rats with myocardial infarction (MI). Rats with MI were intravenously infused with rhNRG-1 (5 mu g/kg/h) for 7 days through osmotic pumps. The mechanism of action of rhNRG-1 was investigated by assaying the non-infarcted myocardium with gene chips. The cMLCK expression, phosphorylated MLC-2v and cardiac function were significantly up-regulated, as assessed by real-time PCR, Western blot and echocardiography, in those animals treated with rhNRG-1. Moreover, the restoration of rhNRG-1-induced sarcomeric organization in serum-free cultured neonatal rat cardiomyocytes with rhNRG-1 was inhibited by cMLCK RNA interference or ML-7, an inhibitor of MLCKs. Adenovirus containing the rat cMLCK coding region was injected into non-infarcted myocardium, and cardiac function was monitored using echocardiography and a haemodynamic machine. The dP/dt and fractional shortening decreasing significantly after MI, and improved by 15.7 and 32.1%, respectively, following local cMLCK application (all P < 0.05). Our results suggest that cMLCK is a downstream effector of rhNRG-1 involved in rhNRG-1-induced cardiac function improvement, and that myocardial cMLCK up-regulation can improve cardiac function in rats with MI.

引用

页码：334 / 343

页数：10

共 34 条

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