Loi H. Cardioprotective effects of metformin in hypoxia and metabolic stress

In the thesis, cardioprotective effects of the antidiabetic medicinal agent metformin and the molecular targets involved in the mechanisms of these properties exerting are explored. It is shown the impact of the drug on the expression of the genes, which take part in the cardiac remodeling process. The experiments performed on the embryonic rat cardiomyoblasts (H9C2 line), exposed to metabolic or hypoxic stress, confirmed the ability of metformin to prevent the development of hypertrophy and apoptosis – the main pathomorphological features which occur in diabetic cardiomyopathy. FохО1- dependent mechanism of anti-apoptotic effect of the drug is investigated as well. It is explored the significance of FохО1 gene expression in the maintenance of normal H9C2 cells size while antihypertrophic effect of metformin is not associated with FoxO1 pathway. In a mouse model of myocardial ischemia-reperfusion, it is established the potency of metformin to prevent cardiac remodeling and fetal genes reprogramming and to attenuate hypertrophy, apoptosis, inflammation and fibrosis. It is investigated that the drug prevents body weight increase, reduces triacylglycerol level in rats which are fed high fat diet (45 %), attenuates hypertrophic and fibrotic remodeling in isoproterenol-induced myocardial injury and decreases BNP serum level both in normal body weight and obesity.