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

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.