Epigenetic Mechanisms of Atherosclerosis Etiopathogenesis

Epigenetic regulation of spatiotemporal gene expression in ontogenesis is determined by programmed species-specific activations of retroelements in successive cell divisions. Evolutionary selection of this genome control mechanism is aimed at achieving a mature state, after which unprogrammed activation of retroelements occurs, which expression products stimulate interferon response, aseptic inflammation and aging-associated diseases development, such as atherosclerosis. Interferon in atherosclerosis stimulates pro-inflammatory macrophage phenotype, which contributes to pathological immune response, foam cell formation and atherosclerosis progression. Activation of retroelements occurs under the influence of viral infections, which role in atherosclerosis development has been proven, which confirms my hypothesis. Dysfunctional foam macrophages produce HERV-K102, which stimulates innate immunity, HERV-K HML2 expression correlates with macrophage immune activation and interferon response. Data were obtained on association with atherosclerosis of microRNAs derived from retroelements, which are involved in the disease pathogenesis due to their influence on cholesterol metabolism (miR-498, -520d), immune processes (miR-1257, -28, -2909), activation of DNMT1 (miR-1264) and EZH2 (miR-630), gene expression in endothelial cells (10 specific miRNAs), vascular smooth muscle cells (14 specific miRNAs) and macrophages (miR-320b, -326, -378, -384), contributing to pathological phenotype of these cells. In atherosclerosis microRNAs derived from retroelements interact with circular RNAs (miR-495, -576, -579, -630, -633, -637, -942) and long non-coding RNAs (miR-326, -4731, -495, - 616, -641, -664a) the key sources of which are retroelements. Role of ANRIL, NEAT1, PAPIA, MAARS, VINAS, H19, AK136714, MIAT, and interaction of Alu elements with ANRIL and NEAT1, identified in atherosclerosis development. The data obtained can become the basis for targeted effect on retroelements activation in atherosclerosis using microRNAs.