Reviews on Clinical Pharmacology and Drug TherapyReviews on Clinical Pharmacology and Drug TherapyОбзоры по клинической фармакологии и лекарственной терапии1683-41002542-1875Eco-Vector4860510.17816/RCF192131-143ReviewsНаучные обзорыReview ArticleDirect cardial effects and mechanisms of cardiovascular action of gliflosinsПрямые кардиальные эффекты и механизмы кардиоваскулярного действия глифлозиновhttps://orcid.org/0000-0002-8101-103X4520-7720ZverevYakov F.ЗверевЯков Федорович
Russian Federation

MD, PhD, Dsci (Medicine), Professor. Tht Deparment of Pharmacology, Altai State Medical University

Доктор медицинских наук, профессор кафедры фармакологии

zveryasha@mail.ruhttps://orcid.org/0000-0002-5889-70714355-8205RykunovaAnna Y.РыкуноваАнна Яковлевна
Russian Federation

PhD, Cand. Sci. (Med.)

кандидат медицинских наук

zveranna@mail.ruAltai State Medical UniversityАлтайский государственный медицинский университетBarnaul Law InstituteБарнаульский юридический институт0908202119213114327102020Copyright ©; 2021, Zverev Y.F., Rykunova A.Y.Copyright ©; 2021, Зверев Я.Ф., Рыкунова А.Я.2021Zverev Y.F., Rykunova A.Y.Зверев Я.Ф., Рыкунова А.Я.http://creativecommons.org/licenses/by/4.0https://journals.eco-vector.com/RCF/article/view/48605

The literature review is devoted to the study of the mechanisms of the cardioprotective action of a new class of glucose-lowering drugs glyflozins, which inhibit the joint transport of sodium and glucose in the proximal renal tubules. Favorable changes in ion transport in cardiomyocytes with the use of these drugs are considered. The inhibition of the activity of the sodium-hydrogen exchanger (NHE) was found, followed by a decrease in the activity of Na+/ Ca2+ exchange on the mitochondrial membranes of the cardiomyocytes, which leads to a decrease in the concentration of Ca2+ in the cytoplasm with a simultaneous increase in mitochondria. This initiates a number of intracellular signaling cascades that contribute to the optimization of mitochondrial homeostasis. The use of glyflozins, apparently, provides a balance between the fusion and fission of mitochondria, which determines the bioenergetic adaptation of the cell to the state of intracellular metabolism, weakens the development of the inflammatory response, fibrosis and oxidative stress in the myocardium, which are activated under conditions of diabetes mellitus. The point of view is discussed, according to which the mechanism of anti-inflammatory action of glyflozins is associated with inhibition of the activity of the NLRP3 inflammasome, which contributes to the progression of myocardial dysfunction and subsequent chronic heart failure. The results of clinical trials and experimental data on the beneficial effect of glyflozins in the development of various phenotypes of heart failure with reduced and preserved ejection fraction are analyzed. The assumption is substantiated about the prospects for wider use of these hypoglycemic drugs in heart failure, which is not limited to diabetes mellitus. The assumptions made require further experimental and clinical studies.

Обзор литературы посвящен исследованию механизмов прямого кардиопротективного действия нового класса сахароснижающих препаратов глифлозинов, ингибирующих совместный транспорт натрия и глюкозы в проксимальных отделах почечных канальцев. Рассматриваются благоприятные изменения ионного транспорта в кардиомиоцитах (КМЦ) при применении этих препаратов. Установлено угнетение активности натрий-водородного обменника (NHE) с последующим снижением активности Na+/Ca2+-обмена на мембранах митохондрий КМЦ, что приводит к уменьшению концентрации Ca2+ в цитоплазме с одновременным ее увеличением в митохондриях. Это инициирует ряд внутриклеточных сигнальных каскадов, способствующих оптимизации митохондриального гомеостаза. Использование глифлозинов, по-видимому, обеспечивает баланс между слиянием и делением митохондрий, что обусловливает биоэнергетическую адаптацию клетки к состоянию внутриклеточного метаболизма, ослабляет развитие воспалительной реакции, фиброза и окислительного стресса в миокарде, активируемые в условиях сахарного диабета. Обсуждается точка зрения, согласно которой механизм противовоспалительного действия глифлозинов связан с угнетением активности инфламмасомы NLRP3, которая вносит вклад в прогрессирование миокардиальной дисфункции и последующей хронической сердечной недостаточности. Анализируются результаты клинических испытаний и данные экспериментальных исследований относительно благоприятного действия глифлозинов в условиях развития различных фенотипов сердечной недостаточности со сниженной и сохраненной фракцией выброса. Обосновывается предположение о перспективах более широкого применения этих сахароснижающих препаратов при сердечной недостаточности, не ограничивающейся лишь сахарным диабетом. Высказанные предположения требуют дальнейших экспериментальных и клинических исследований.

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