Epigenetic Mechanisms of the Influence of Physical Activity on the Development of Atherosclerosis

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Abstract

This work is an analytical review dedicated to the search for driver mechanisms of epigenetic changes in atherosclerosis pathogenesis. The disease affects the cardiovascular system in the adult population, mainly the elderly and senile. Atherosclerosis is accompanied by progressive deposition of cholesterol and lipoproteins in vessels intima with inflammation, narrowing of the lumen and impaired blood supply to tissues and organs. These processes are characterized by changes in the expression of CACNA1C, GABBR2, TCF7L2, DCK, NRP1, PBX1, FANCC, CCDC88C, TCF12, ABLIM1 genes. Prevention of atherosclerosis is physical activity, the mechanisms of which are not fully understood. Experimental models have shown that regular training not only has a protective effect on the development of atherosclerosis, but also inhibits the progression of an already developed disease with a decrease in vascular stenosis, an increase in the concentration of collagen and elastin and matrix metalloproteinases in plaques. These results have been confirmed by clinical studies. The purpose of this review was to systematize the accumulated results on the causes of epigenetic changes, including those under the influence of regular training, causing changes in the expression of specific microRNAs in atherosclerosis. It was found that physical exercise in Apo-/- mice increases the expression of miR-126 and miR-146a (inhibiting the TLR4 and TRAF genes), miR-20a (affecting PTEN), miR-492 (suppressing RETN gene mRNA). Clinical studies have shown an increase in the levels of miR-146a, miR-126, miR-142-5p, miR-424-5p and a decrease in the transcription of miR-15a-5p, miR-93-5p, miR-451 under the influence of aerobic training. It has been suggested that the drivers of epigenetic changes in atherosclerosis are transposons pathologically activated during aging, the transcription of which can change under the influence of physical training, which is accompanied by impaired expression of long non-coding RNAs and microRNAs derived from transposons. Analysis of the literature data allowed us to identify 36 such microRNAs, 25 of which showed identical changes in levels during aging and atherosclerosis.

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About the authors

R. N. Mustafin

Bashkir State Medical University

Author for correspondence.
Email: ruji79@mail.ru
Russian Federation, Ufa, 450008

E. K. Khusnutdinova

Institute of Biochemistry and Genetics Ufa Federal Research Centre, Russian Academy of Sciences

Email: ruji79@mail.ru
Russian Federation, Ufa, 450054

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Supplementary files

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2. Fig. 1. Scheme of the role of microRNA in the mechanisms of atherosclerosis development.

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3. Fig. 2. Schematic representation of the effects of physical exercise on the expression of microRNAs involved in the pathogenesis of atherosclerosis.

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4. Fig. 3. Scheme of interaction of mobile genetic elements with non-coding RNA (ncRNA) in the pathogenesis of atherosclerosis.

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