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 in vitro effects of IMD1‑53 on angiogenesis and the in vivo 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.