Direct cardial effects and mechanisms of cardiovascular action of gliflosins

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Abstract

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.

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About the authors

Yakov F. Zverev

Altai State Medical University

Author for correspondence.
Email: zveryasha@mail.ru
ORCID iD: 0000-0002-8101-103X
SPIN-code: 4520-7720

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

Russian Federation, 40 Lenina str., 656038, Barnaul

Anna Y. Rykunova

Barnaul Law Institute

Email: zveranna@mail.ru
ORCID iD: 0000-0002-5889-7071
SPIN-code: 4355-8205

PhD, Cand. Sci. (Med.)

Russian Federation, Barnaul

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