Intermedin1-53 enhances angiogenesis and attenuates adverse remodeling following myocardial infarction by activating AMP-activated protein kinase

被引:19
作者
Chen, Kankai [1 ]
Yan, Meiling [1 ]
Li, Yongguang [1 ]
Dong, Zhifeng [1 ]
Huang, Dong [1 ]
Li, Jingbo [1 ]
Wei, Meng [1 ]
机构
[1] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Cardiol, 600 Yishan Rd, Shanghai 200233, Peoples R China
基金
中国国家自然科学基金;
关键词
intermedin; myocardial infarction; ventricular remodeling; angiogenesis; Lambda MP-activated protein kinase; CARDIAC-FUNCTION; ISCHEMIC-MYOCARDIUM; PRESSURE-OVERLOAD; HYPERTROPHY; CARDIOMYOCYTE; DYSFUNCTION; STRESS; INJURY;
D O I
10.3892/mmr.2017.6193
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Adverse ventricular remodeling is a maladaptive response to acute loss of myocardium and an important risk factor for heart failure following myocardial infarction (MI). Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide family, which may possess potent cardioprotective properties. The aim of the present study was to determine whether IMD1-53, a mature bioactive form of IMD, may promote therapeutic angiogenesis within the infarcted myocardium, therefore attenuating adverse ventricular remodeling post-MI. The present study observed that treatment with IMD1-53 promoted proliferation, migration and tube formation of primary cultured myocardial microvascular endothelial cells (MMVECs). In a rat model of MI, chronic administration of IMD1-53 increased capillary density in the peri-infarct zone, attenuated ventricular remodeling and improved cardiac performance post-MI. Treatment with IMD1-53 also significantly increased the expression levels of phosphorylated-AMP-activated protein kinase (AMPK) and the subsequent activation of endothelial nitric oxide synthase in MMVECs and post-MI rat myocardium, without a significant influence on the expression of vascular endothelial growth factor. Notably, the initro effects of IMD1-53 on angiogenesis and the invivo effects of IMD1-53 on post-MI ventricular remodeling were largely abrogated by the co-administration of compound C, an AMPK inhibitor. In conclusion, the present study demonstrated that IMD1-53 could attenuate adverse ventricular remodeling post-MI via the promotion of therapeutic angiogenesis, possibly through the activation of AMPK signaling.
引用
收藏
页码:1497 / 1506
页数:10
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