Portnichenko G. The participation of sterol-regulatory proteins (SREBP) in regulation of morphofunctional state of cardiovascular system in hypertensive rats under high cholesterol diet.

The dissertation is aimed to the study of the combined effect of hypertension and high cholesterol diet on the function and structure of the cardiovascular system, in particular of the heart and large vessels, as well as lipid metabolism and expression of the sterol regulatory elements (SREBP) - one of the key regulators of free fatty acids and cholesterol synthesis in the cell. For the first time, the effect of a high cholesterol diet under hypertension was investigated in comparison with the influence of each of these factors separately. The development of the initial stages of atherogenic changes in the wall of the aorta of rats is described for the first time. The microcatheterization of the left ventricle of the heart showed changes in the functioning of the cardiovascular system under the influence of hypercholesterolemia and arterial hypertension. Determination of blood lipoprotein levels showed changes in the normal state of lipid metabolism due to the effect of a high cholesterol diet that was, however, less pronounced under hypertension. Another part of the work was the study of genetic mechanisms of lipid metabolism regulation using real-time PCR, which established changes in the expression of key regulators of the synthesis of fatty acids and cholesterol in the cell SREBF1 and SREBF2, as well as the expression of their target genes Insig1 and HMGcoAr. The obtained data indicate a violation of the lipids genesis normal regulation in cells under the combined effect of hypertension and hypercholesterolemia conditions, both in the cardiovascular system and in liver cells, and also testifies to the disorder between the processes of consumption and synthesis of lipids de novo, as one of the leading links of lipid metabolism disorders. Histological and ultrastructural studies of the tissues of the heart and blood vessels showed hypertensive-induced changes in the ultrastructure of the aortic walls, which have significantly deteriorated due to disorders of the lipid metabolism, and show a pattern typical of the atherogenesis initial stages. Thus, it has been shown for the first time that the combined effect of a high cholesterol diet and arterial hypertension is interrelated due to action on regulatory mechanisms, which creates the preconditions for more severe disorders specific for metabolic syndrome.