Effect of ghrelin on hypoxia-related cardiac angiogenesis: involvement of miR-210 signalling pathway.

Objective: Hypoxia is the main stimulus for angiogenesis. Hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), and miR-210 are involved in the hypoxia-induced angiogenesis. This study examined the effects of hypoxia and/or ghrelin on miR-210, HIF-1α, and VEGF levels in the heart of rats. Methods: Wistar rats were randomly divided into 4 groups (n = 6): control; ghrelin, received daily intraperitoneal injections of ghrelin; hypoxia, was exposed to hypoxic condition; hypoxia + ghrelin, was exposed to hypoxic condition and received intraperitoneal injections of ghrelin, for 2 weeks. Myocardial angiogenesis, the expression level of miR-210, and protein levels of HIF-1α and VEGF were assayed in the heart samples. Results: Hypoxia increased myocardial angiogenesis and cardiac levels of miR-210, HIF-1α, and VEGF. However, ghrelin inhibited these hypoxia-induced changes. Interestingly, ghrelin had no significant effect on miR-210, HIF-1α, and VEGF levels in normoxic condition. Conclusion: Ghrelin may be useful as an anti-angiogenic factor.