THE ROLE OF VEGF SINGLE NUCLEOTIDE POLYMORPHISMS IN THE DEVELOPMENT OF CARDIOVASCULAR DISEASES

Cardiovascular diseases (CVD) are the main cause of mortality in the population. The pathophysiological processes underlying the development of CVD are inflammation, endothelial dysfunction, oxidative stress, atherosclerosis, fibrosis, dyslipidemia and thromboembolism. Endothelial dysfunction affects the balance of endothelium-dependent vasoconstriction and vasodilation by increasing cytokine levels, adhesion molecule expression, leukocyte and monocyte migration, and platelet activation.

The vascular endothelial growth factor (VEGF) family is an important component of angiogenesis involved in inducing migration and proliferation of endothelial cells by modulating vascular permeability and thrombogenicity. The VEGF family includes 5 proteins, of which VEGF-A, VEGF-B and PlGF (placental growth factor) regulate angiogenesis, and VEGF-C and VEGF-D (c-Fos-induced growth factor, FIGF) regulate lymphangiogenesis.

VEGF-A is a key factor in the angiogenesis and collateral circulation (arteriogenesis) mediated by the binding of VEGF-A to the VEGFR-1 (Flt-1) and VEGFR-2 (KDR) receptors. As a result of the research, data were obtained on an increased risk of coronary heart disease in the case of detection of VEGF-A single nucleotide polymorphisms (SNPs), particulary rs3025039, rs699947, rs2010963, rs1570360 and rs7667298.

VEGF-D is a secreted factor that regulates lymphangiogenesis, angiogenesis, and endothelial proliferation through interaction with VEGFR2 (KDR). Studies have demonstrated an increase in VEGF-D levels caused by rs192812042 and rs234500 polymorphisms in patients with acute and chronic coronary syndromes, which indicates the role of VEGF-D in the formation of CVR by involving lymphangiogenesis, as well as modulating angiogenesis.

Genotyping of patients with CVR with subsequent identification of VEGF SNP will allow timely identificate groups of patients with an initially increased risk of developing cardiovascular pathology and prescribe treatment and measures, prevent the development of acute cardiovascular pathology and reduce mortality caused by CVD.

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