Gurianova V. MicroRNA-1 upon Experimantal Cardiac Pathology of Different Etiology.

We used thecombination of classic methods of pathophysiology and contemporary techniques of molecular biology to determine the particularities of microRNA-1 biogenesis in rat cardiomyocytes upon anoxia-reoxygenation in culture, myocardial infarction and post-myocardial infarction heart remodeling in vivo, and cardiac dysfunction in aged hypertensive rats. These data demonstrate the importance of microRNA-1 posttranscriptional regulation and provide the evidence for the future detailed investigation of these phenomena upon cardiac pathology and its correction. Furthermore, we were the first to find that knockdown of lipoxygenase 5 provokes the decrease of mature microRNA-1 in cardiomyocytes; and the analysis of immature microRNA-1 let us suppose the alteration of cytoplasmic level of maturation as a cause of decreased microRNA-1. Proteasome inhibitor provokes microRNA-1 increase in intact culture, probably, due to its stabilization; however, this we have not observed this effect in culture undergone the anoxia. We were the first to show that mature and primary but not precursor microRNA-1 can be the substrate for endonuclease activity of proteasome in vitro. The combination of chronic high blood pressure and especially ageing leads to alterations in microRNA-1 biogenesis: decreased level of mature microRNA-1 associates with accumulation of its primary and especially precursor forms. It could play an essential role in heart ageing and cardiac dysfunction upon high blood pressure.