Surova O. Expression of endogenous cardioprotection genes at ischemia-reperfusion of heart.

Dissertation is devoted to the study of role of genetic factors in development of pathological processes, which result in death of cardiomyocytes (by necrosis, apoptosis and autophagy), stipulate stability of myocardium to the hypoxia and other pathogenic factors, roles of genes of stress proteins at myocardial ischemia-reperfusion and anoxia-reoxygenation of neonatal cardiomyocytes culture, and also to participation of these factors in the mechanisms of pre- and postconditioning. The information about the role of changes of expression of genes FRAP, Bcl-2, HIF-3alpha, HSP70 and HSP90 in realization of the programs of endogenouscardioprotection is received at modern methodological level. The cytoprotective effects of late ischemic pre- and postconditioning are investigated. It was showh that preconditioning in a remote period prevents apoptotic death of cardiomyocytes in a culture at the first episode of anoxia-reoxygenation, and at its second episode - diminishes population of necrotic cells. The decrease of expression of genes of heat shock proteins HSP70 and HSP90, regulators of apoptosis and autophagy Bcl2 and FRAP was observed, while the expression of HIF-3alpha was increased at these conditions. Late postconditioning did not provide the stability of cardiomyocytes to the damaging action of anoxia-reoxygenation , the number of necrotic cardiomyocytes was dramatically increased. The expression of genes of HSP70 and HSP90 was reduced and a tendency to the increase of Bcl2 and FRAP expression was observed, we also established powerful decline of HIF-3alpha expression at late postconditioning modeling. The possibility late pharmacological preconditioning modeling with the use of proteasome inhibitor is examined. It was shown that proteasome inhibitor in a concentration 100 nM prevents death of cardiomyocytes by apoptosis and necrosis at anoxia-reoxygenation modeling. We also investigated the changes of gene expression in heart tissue at ischemia-reperfusion modeling in vivo. The possible cardioprotective role of genes of heat shock proteins is set at miocardial ischemia-reperfusion- reliable negative correlation is set statistically between intensity of HSP70 gene expression and the size of infracted area at rat coronary vessel occlusion.