В обзоре приведены сведения о роли ДЭ в патогенезе ССЗ как ведущей при-чины смертности. Рассмотрена морфофункциональная характеристика эндоте-лия, продукты синтеза и их регуляторы. Выделена регуляторная роль NO и его эффекты, пути синтеза в эндотелии, ферментативные системы. Приведена характеристика NO-синтазы и полиморфизмов гена, её кодирующего, а также рассмотрена их клиническая значимость в аспекте развития ДЭ. Определены механизмы баланса вазодилататоров и вазоконстрикторов, к которым отно-сятся и ЭТ, имеющие разнообразные функции. Полиморфность генотипа опре-деляет активность ЭТ-1, что имеет существенное значение в патогенезе ГБ, ЭД, ИБС и взаимосвязано с продукцией NO. Показаны генетические основы регуля-ции ренин-ангиотензин-альдостероновой системы при участии АПФ и вклад редких полиморфизмов в повышение риска развития ИБС, инфаркта миокарда, диабетической нефропатии. Патогенетическая значимость ДЭ в условиях окис-лительного стресса определяет внимание клиницистов к этой патологии, тесно связанной с атеросклерозом, а молекулярные и генетические аспекты форми-рования ССЗ диктуют необходимость применения персонализированной меди-цины для прогнозирования и профилактики, а фармакогенетики -для коррек-ции патологии эндотелия и сердечно-сосудистой системы в целом. ENDOTHELIAL DYSFUNCTION AS CORNERSTONE OF CARDIOVASCULAR EVENTS: MOLECULAR AND PHARMACEUTIC ASPECTSKireeva V. V. The review concerns on the data about ED in CVD pathogenesis as the leading cause of death. The morphofunctional characteristic of endothelium is discussed, its synthetic activity and regulators. Also the regulatory role of NO-synthase and its gene polymorphism, as their clinical significance as the ED development factors. Also the vasodilator and vasoconstrictor balancing mechanisms of ET, showing different functions. Polymorphism of genes influences ET-1 activity, that has significant value for RAAS regulation with ACE and the influence of rare polymorphisms in CHD risk, MI, diabetic nephropathy. Pathogenetic significance of ED in the conditions of oxidative stress defines clinicists attention on this pathology, related to atherosclerosis, and molecular and genetic aspects of CHD formation do dictate inevitability of personalized medicine for prognosis and prevention, as pharmacogenomics -for endothelial pathology correction of cardiovascular system in general. Russ

Purpose of the study. To test the functional associations of polymorphic variants of genes in the regulation of blood pressure and vascular tone in employees of the ISC SB RAS. Materials and methods. The study involved patients, employees of the ISC SB RAS, being under care of the outpatient clinic of the Hospital of the ISC SB RAS. During routine laboratory testing the patients were taken 2 ml of blood for genetic analysis and further molecular genetic study on “Hypertension”, “Endothelial dysfunction”, “Pharmacogenetics”, “Inflammatory response” panels. Results. In the analysis of 12 genes coding for key proteins of hormonal enzyme blood pressure regulation systems, polymorphism of CYP11B2 showed statistically significant correlation with the presence of arterial hypertension, which makes its further study promising. The presence of allele C showed protective significance in relation to the development of hypertension with OR = 0,247. When checking associations of functional polymorphic variants of genes, the products of which are involved in the regulation of vascular tone, with hypertension in patients younger than 50 years old we found association of T/T rs5443GNB3 genotype with the debut of hypertensive disease under the age of 50. The data obtained allow the doctor to choose the most personalized and effective safe drug from certain groups, as well as its dose for employees having passed molecular genetic testing. These data can reveal predisposition to the most widespread and socially significant diseases in the surveyed subjects and provide specific personalized recommendations for the prevention of these diseases.

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