Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences66717310.31857/S0016675824100014wgfnmrОБЗОРНЫЕ И ТЕОРЕТИЧЕСКИЕ СТАТЬИReview ArticleEpigenetic Mechanisms of the Influence of Physical Activity on the Development of AtherosclerosisЭпигенетические механизмы влияния физической активности на развитие атеросклерозаMustafinR. N.МустафинР. Н.
Russian Federation
ruji79@mail.ruKhusnutdinovaE. K.ХуснутдиноваЭ. К.
Russian Federation
ruji79@mail.ruBashkir State Medical UniversityБашкирский государственный медицинский университетInstitute of Biochemistry and Genetics Ufa Federal Research Centre, Russian Academy of SciencesИнститут биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наук16102024601032126022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0016-6758/article/view/667173

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.

Данная работа является аналитическим обзором, посвященным поиску драйверных механизмов эпигенетических изменений в патогенезе атеросклероза. Заболевание поражает сердечно-сосудистую систему у взрослого населения, главным образом пожилого и старческого возраста. Атеросклероз сопровождается прогрессирующим отложением в интиме сосудов холестерина и липопротеинов с воспалением, сужением просвета и нарушением кровоснабжения тканей и органов. При этом меняется экспрессия генов CACNA1C, GABBR2, TCF7L2, DCK, NRP1, PBX1, FANCC, CCDC88C, TCF12, ABLIM1. Профилактикой атеросклероза является физическая нагрузка, механизмы реализации которой до конца не изучены. На экспериментальных моделях показано, что регулярные тренировки оказывают не только протективное действие на развитие атеросклероза, но также ингибируют прогрессирование уже развившейся болезни с уменьшением стеноза сосудов, повышением концентрации в бляшках коллагена и эластина, матриксных металлопротеиназ. Полученные результаты были подтверждены клиническими исследованиями. Целью настоящего обзора было систематизировать накопленные данные о причинах эпигенетических изменений, в том числе под влиянием регулярных тренировок, вызывающих изменение экспрессии специфических микроРНК при атеросклерозе. Выявлено, что физические упражнения у Apo-/- мышей повышают экспрессию miR-126 и miR-146a (ингибирующих гены TLR4 и TRAF), miR-20a (воздействующая на PTEN), miR-492 (подавляющая мРНК гена RETN). Клинические исследования показали увеличение уровней miR-146a, miR-126, miR-142-5p, miR-424-5p и снижение транскрипции miR-15a-5p, miR-93-5p, miR-451 под влиянием аэробных тренировок. Сделано предположение, что драйверами эпигенетических изменений при атеросклерозе являются патологически активированные при старении транспозоны, транскрипция которых может меняться под влиянием физических тренировок, что сопровождается нарушением экспрессии произошедших от транспозонов длинных некодирующих РНК и микроРНК. Анализ литературных данных позволил выявить 36 таких микроРНК, для 25 из которых показано идентичное изменение уровней при старении и атеросклерозе.

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