The role of single nucleotide polymorphisms of VEGF gene in the development of cardiovascular diseases

Cardiovascular diseases (CVD) are the main cause of mortality in general population. Pathophysiology underlying CVD development includes 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 blood clotting. 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 our search, an increased risk of coronary heart disease is expected in the case of detection of certain single oligonucleotide polymorphisms (SNPs) in VEGF-A gene, in particular: rs3025039, rs699947, rs2010963, rs1570360 and rs7667298. VEGF-D is a secreted factor that regulates lymphangiogenesis, angiogenesis, and endothelial proliferation through interaction with VEGFR2 (KDR). Some studies have demonstrated an increase in VEGF-D levels caused by rs192812042 and rs234500 polymorphisms in patients with acute and chronic coronary syndromes, thus suggesting the role of VEGF-D in the formation of CVD by involving lymphangiogenesis, as well as modulating angiogenesis. Genotyping of patients at CVD risk with identification of multiple VEGF SNPs will enable timely diagnostics of patients with initially increased risk of developing cardiovascular pathology and prescribe treatment and measures, prevent development of acute cardiovascular pathology and reduce mortality caused by CVD.

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