Kuzmenko M. Systemic and molecular genetic mechanisms of cardiac remodeling and its experimental therapy using bioflavonoids

The thesis deals with the mechanisms of cardiac remodeling after coronary artery occlusion and isoproterenol infusion and determines the possibilities of correction of the pathological process by bioflavonoids. For the first time we used the method of pressure-volume loops in rats in vivo that was supplemented by histological and molecular genetic methods. A detailed study is performed and comparative characteristics of the pump, diastolic and contractile function of rat heart with injury of various origins are given. The extent of protective mechanisms was established - from the mRNA level of genes encoding protective (natriuretic) proteins and their receptors to the manifestation of cardiogenic depressor reflex reaction. It is shown that the pump dysfunction is associated mainly with fibrosis and diastolic impairment of the heart in both types of damage in a month. Signs of diastolic dysfunction is more pronounced after isoproterenol damage, which correlated with more significant fibrosis of the heart (14,6 ± 1,5% of the area of the left ventricle) to 7,73 ± 2,3% after coronary artery occlusion (p<0,05). At the same time, in animals with significant fibrosis the increase in contractile function is observed, which, in our opinion, serves as compensatory reaction. For the first time it is shown that the response of the genetic apparatus of cardiac cells after coronary artery occlusion and isoproterenol infusion differs significantly in its intensity: the gene expression level of natriuretic peptides and their receptors is significantly higher in the first case. For the first time the restoring (protective) action of bioflavonoids against manifestation of pathological cardiac remodeling is demonstrated. Combined use of Corvitin and Kvertyn reduces fibrotic remodeling, myocardial stiffness, improves diastolic and pump function of the heart. Key words: cardiac remodeling, gene expression of natriuretic peptides, gene expression of receptors of natriuretic peptides, pressure-volume loops, isoproterenol, coronary artery occlusion, heart failure, bioflavonoids.