Angiotensin II

Angiotensin II is one of the most powerful vasoconstrictors, which determines its role in the pathogenesis of arterial hypertension. Through the receptor AT II type 1 mediated induction of cell growth. The effect of angiotensin II on this receptor subtype mediates an increase in the expression of such proliferation factors as platelet-derived growth factor and the main growth factor of fibroblasts, as well as the antiproliferative factor b1. Recent studies have shown that angiotensin II also induces endothelin 1 and insulin-like growth factor. Thus, changes in the expression or structure of an ATII type 1 receptor due to the polymorphism of its gene can lead to changes in the regulation of vascular tone or proliferation of elements of the vascular wall,therefore, the type 1 angiotensin II receptor gene is considered as one of the candidate genes associated with the pathology of the cardiovascular system.

When studying the mRNA level, it was shown that the expression level of the AT2P1 receptor gene reduces the introduction of exogenous nitrates, and in addition, it was shown that the expression level of the gene decreases with the use of estrogens. An increase in the expression of the AT2P1 gene is observed with hyperinsulinemia, with an excessive salt load .

More than 10 types of polymorphism of the AT2P1 gene promoter region have been described. The most commonly studied polymorphism of the A1166C mutation. It was first described and analyzed in Bonnardeaux et al., Where the frequencies of the A1166C polymorphism alleles were studied in the white European population in patients with arterial hypertension, healthy people with relatives, patients with hypertension and in the control group. The polymorphic marker A1166C, based on the variability of the bases of A (adenine) and C (cytidine) in the 1166th position of the nucleotide sequence of the gene is located in 3 “- the untranslated region of the AT1P gene located on the chromosome 3g 21-g25. In Bonnardeaux et al. ., a significantly higher frequency of the C allele was shown in groups 1 and 2.that in patients with arterial hypertension there is a significant increase in the content of the allele carrying in position 1166 cytidine.

In addition to the genes encoding the main protein components of the renin-angiotensin system, the genes encoding the structure of substances that affect the expansion of the lumen of the blood vessels are of no less interest. Such a substance is, in particular, nitric oxide (NO) – an endothelial relaxation factor that plays an important role in the regulation of vascular tone (vasodilation) and thrombogenesis. A decrease in the NO content leads to disruption of the normal activity of the vessels and vasomotor organs, an increase in the processes of thrombus formation and atherogenesis. NO is produced from L-arginine with the participation of the NO synthase enzyme. There are three known forms of this enzyme encoded by different genes. Endothelial NO synthase is a product NOS3 gene located on chromosome 7q 35-36. Among the genes encoding NO synthase, the most likely candidate for participation in the development of cardiovascular diseases is the NOS3 gene.

In intron 4 of this gene, there is an ecNOS4a / 4b minisatellite, consisting of two alleles, which consist of 4 (allele 4a) or 5 (allele 4b) tandem repeats of 27 bp in size. In the population, the allele with five repetitions is much more common than with four. In individuals homozygous for the rare allele, the level of nitrates and nitrites in the blood is increased, directly related to the rate of NO production by the vascular endothelium, which indicates the potential genetic role of the genotype 4a / 4a as a risk factor for the development of atherosclerosis and diseases leading to to disruption of normal NO production.

In identifying a group of patients with arterial hypertension and left ventricular hypertrophy, the frequency of occurrence of allele a was significantly higher than in the group of healthy individuals .

local_offerevent_note August 6, 2019

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