Apelin protects the heart against ischemia-reperfusion injury via epidermal growth factor receptor (EGFR) transactivation

Apelin peptide is a ligand of the G protein coupled receptor (GPCR) APJ. Apelin-13 (Ape) is the most active isoform on the cardiovascular system, where it exerts positive inotropy and vasodilation. It also mimics ischemic postconditioning (IPost) against ischemia–reperfusion (I/R) injury. Protection is caused by NO after phosphatidylinositol 3-kinase (PI3K)-Akt activation. Various GPCRs activate PI3K-Akt via epidermal growth factor receptor (EGFR) transactivation by ligand-dependent and -independent pathways, the former due to the shedding of epidermal growth factor (EGF)-like ligands by matrix metalloproteinase (MMP), the latter to the nonreceptor tyrosine kinase Src. We investigated the main steps of the pathway of Apeinduced cardioprotection focusing the attention on a possible role of EGFR transactivation.