Альдостеронсинтаза, поліморфізм її гена CYP11B2 при артеріальній гіпертензії і асоційованих з нею кардіоваскулярних захворюваннях (огляд літератури)

The article presents the data of foreign and national literature on the pathogenetic role of aldosterone (AL), levels of aldosterone synthase (AS) and gene polymorphisms of this enzyme in patients with various forms of arterial hypertension, associated with diseases of the heart and vessels, such as hypertrophic cardiomyopathy, atrial fibrillation, brain pathology etc. The activation of circulating and local renin-angiotensin system results in increased secretion of the powerful vasoconstrictor angiotensin II, which stimulates AL production in an auto- and paracrine way. Angiotensin II and AL have independent regulatory effect on the function and structure of the heart and blood vessels, kidneys and brain. Both hormones stimulate hypertrophy of cardiomyocytes and vascular smooth muscle cells, hyperplasia of myocardial fibroblasts, synthesis of connective tissue matrix. As a result, the left ventricular hypertrophy is formed, cardiac remodeling is progressing, in which processes AL is involved. The main humoral, metabolic, cellular, immune-inflammatory and profibrogenic effects of aldosterone are considered. The AS gene CYP11B2 catalyzes the last stage of the synthesis of AL from desoxycorticosterone. The gene is located in the g21 region of chromosome 8, and consists of nine exons and eight introns. Single nucleotide polymorphisms are known in the promoter region of AL and in the AS gene. The polymorphism of the 5th section of this gene, which manifests itself by replacing cytosine (C) with thymine (T) at the 344th position of the 344 T/C nucleotide sequence, rs1799998, has been most fully investigated. MiR-766 can be used to suppress the expression of the AS gene in an experiment, as well as in humans, and reduce blood pressure level in people having the –344T allele. The determination of the single nucleotide replacement of T by C at position 344 of the CYP11B2 gene is carried out by polymerase chain reaction with polymorphism of the length of restriction fragment analysis. Currently, a list of forward and reverse primers, which are used in the amplification of the CYP11B2 gene, has been compiled. In the number of studies, the relationship between AS gene polymorphism and risk factors of cardiovascular and endocrine pathology were studied, the sex, gender and ethnic characteristics of AS gene polymorphism were considered, and the results of population studies of gene polymorphism of AS in several European and Asian countries were received. The information is provided on the AS levels and gene polymorphisms of this enzyme in arterial hypertension, including its resistant form, in the combination of ischemic heart disease, postinfarction cardiosclerosis, their participation in cardiovascular remodeling, the formation of left ventricular hypertrophy, in hypertensive nephropathy, cerebral stroke, heart failu­re. The levels of AL and gene polymorphism of AS also can be used as differential diagnostic criteria for hypertension with low plasma renin activity, with renovascular and resistant hypertension, at hyperaldosteronism types 1 and 2, aldosteromas, apparent mineralocorticoid excess syndrome, congenital adrenal hyperplasia. The congenital defects of enzymatic activity of AS, insufficiency of AS and aldosteronism (arterial hypertension), which are cured by glucocorticoids, are described. The results of several studies provide conflicting data on the degree of response to antihypertensive therapy by various first-line drugs and mineralocorticoid receptor antagonists, depending on the haplotype CYP11B2, are presented. The prospects of therapeutic use of a new class of drugs — aldosterone synthase inhibitors among various categories of patients with symptoms of arterial hypertension are considered.