Cardioprotective effect of hypoxic preconditioning and its signaling mechanisms

High hospital mortality in acute myocardial infarction (AMI) and the lack of its improvement in recent years necessitate the development and implementation of new approaches to AMI treatment, including those aimed at reducing ischemiareperfusion (IR) injury. The development of these approaches can be facilitated by studying the molecular mechanisms of acute adaptation to hypoxia (hypoxic preconditioning, HP). HP has infarction-limiting and vasoprotective effects, and improves contractile function recovery during cardiac reperfusion; it also reduces IR-induced cardiomyocyte apoptosis. The cardioprotective effect of HP is mediated through the activation of Gi/o- and Gq/I1-coupled receptors (adenosine, apelin, muscarinic, and nicotinic) and associated with intracellular enzymes: heme oxygenase-1, inducible NO synthase, protein kinase C, phosphatidylinositol 3-kinase, Akt kinase, AMP-activated protein kinase, p38 kinase. Data series suggest that HP triggers include the generation of reactive oxygen and the opening of the mitochondrial ATP-sensitive K + channel, preconditioning also prevents their excessive production during reperfusion. HP-induced cardiac tolerance to IR is mediated by heat shock proteins and transcription factors (HIF-1α, Nrf2, GATA-4). Hypoxic postconditioning is a promising intervention for clinical use; however, its effectiveness and mechanisms are poorly understood.