Apelin is Peptide Increasing Tolerance of Organs and Cells to Hypoxia and Reoxygenation. The Signaling Mechanism

Over the last three decades, treatment of stroke and acute myocardial infarction (AMI) has been improved, but it has stagnated in the last few years. Patients with stroke and AMI are admitted with formed ischemic injury of the brain or the heart, thereby it is difficult to affect this injury. However, it was possible to affect reperfusion injury of the brain or the heart. Ischemic damage to the lung is observed in pulmonary embolism. Ischemia and reperfusion of kidneys are observed in kidney transplantation. Significant progress in an increase in the efficacy of kidney transplantation, in treatment of stroke, pulmonary embolism, and AMI can be achieved through the development of novel drugs capable of preventing reperfusion injury of the brain or the heart with high efficiency. Synthetic apelin analogues with a long half-life could be prototypes of such drugs. It was found that apelins can increase tolerance of the heart, the brain, the lung, and the intestine to ischemia/reperfusion (I/R). Protein kinases are involved in the neuroprotective, cardioprotective, renoprotective, and pulmonoprotective effects of apelins. Mitochondrial permeability transition pore and ATP-sensitive K⁺ channels are also involved in the protective effects of apelins. Apelins inhibit apoptosis and ferroptosis. Apelins activate autophagy of cardiomyocytes. Enzyme-resistant apelin analogues are perspective peptides for treatment of AMI, stroke, and I/R injury of lungs and kidneys.