Cardioprotective Effect of Apelin and Apela: The Receptor and Signaling Mechanism

The development of new approaches for the treatment of acute myocardial infarction (AMI) remains a major goal of modern medicine. The objective of the review is an analysis of data on the signaling mechanism of apelin-induced cardiac tolerance to ischemia/reperfusion (I/R). There is evidence that apelin and apela act as autocrine and paracrine factors rather than circulating hormones with a short in vivo half-life. Apelin and apela increase cardiac tolerance to I/R. These peptides decrease infarct size and improve recovery of ventricular function in reperfusion. Apelin activates three signaling pathways: Gi/o protein dependent, Gq/11 protein dependent, and β-arrestin mediated. All three pathways could be involved in the cardioprotective effect of apelin. The following enzymes mediate apelin-induced cardioprotection: NO-synthase (NOS), epidermal growth receptor kinase, phospholipase C (PLC), protein kinase C (PKC), phosphoinositide 3-kinases (PI3K), Src kinase, Akt kinase (Akt), AMP-activated protein kinase (AMPK), guanylyl cyclase (GC), and extracellular signal-regulated kinase (ERK). ATP-sensitive K+ channel (KATP channel) opening and mitochondrial permeability transition (MPT) pore closure may also be involved in apelin-induced cardiac tolerance to I/R. Apelin and apela molecules may form the basis for the creation of new drugs for the treatment of AMI.