diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM12541diaendo-12541Research ArticleОбзорыReviewКардиопротективные механизмы ингибиторов натрий-глюкозного котранспортера 2 типаCardioprotective mechanisms of sodium-glucose cotransporter 2 inhibitorshttps://orcid.org/0000-0003-1316-5245МкртумянА. М.MkrtumyanA. M.

Мкртумян Ашот Мусаелович, доктор медицинских наук, профессор

Москва

eLibrary SPIN: 1980-8700

Ashot M. Mkrtumyan, MD, PhD, Professor

Moscow

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vagrashot@mail.ruhttps://orcid.org/0000-0002-8798-887XМарковаТ. Н.MarkovaT. N.

Маркова Татьяна Николаевна, доктор медицинских наук, доцент, профессор

123182, Москва, ул. Пехотная, д. 3

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Tatyana N. Markova, MD, PhD, Professor

3 Pehotnaja street, 123182 Moscow

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markovatn18@yandex.ruhttps://orcid.org/0000-0001-8270-5626МищенкоН. К.MishchenkoN. K.

Мищенко Надежда Константиновна, аспирант

Москва

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Nadezhda K. Mishchenko, PhD student, endocrinologist

Moscow

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koc-nadushka@yandex.ruМосковский государственный медико-стоматологический университет имени А.И. ЕвдокимоваMoscow State University of Medicine and Dentistry named after A.I. EvdokimovМосковский государственный медико-стоматологический университет имени А.И. Евдокимова; Городская клиническая больница № 52РоссияMoscow State University of Medicine and Dentistry named after A.I. Evdokimov; City Clinical Hospital №52Russian Federation202129062021243291299Copyright © Мкртумян А.М., Маркова Т.Н., Мищенко Н.К., 20212021Мкртумян А.М., Маркова Т.Н., Мищенко Н.К.Mkrtumyan A.M., Markova T.N., Mishchenko N.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/12541

Результаты крупных международных исследований по оценке сердечно-сосудистой безопасности ингибиторов натрий-глюкозного котранспортера 2 типа (иНГЛТ-2) продемонстрировали выраженный кардиопротективный эффект данной группы сахароснижающих препаратов. В статье отражены возможные механизмы положительного влияния иНГЛТ-2 на сердечно-сосудистую систему, включающие в себя гемодинамические и внутриклеточные эффекты (метаболические эффекты и электролитные изменения); а также влияние на маркеры сердечно-сосудистых заболеваний (ССЗ). Гемодинамические эффекты иНГЛТ-2 характеризуются снижением преднагрузки и постнагрузки на миокард благодаря осмотическому диурезу, уменьшению уровня артериального давления (АД) и жесткости сосудистой стенки. Метаболические эффекты данной группы препаратов сопровождаются повышением продукции кетоновых тел с последующим увеличением синтеза молекул аденозинтрифосфата (АТФ) и улучшением энергетического обмена в кардиомиоцитах. Также иНГЛТ-2 модифицируют работу ионных транспортеров (NHE1 и NHE3). Уменьшение концентрации ионов натрия и кальция в цитозоле и повышение уровня кальция в митохондриях кардиомиоцитов способствуют усилению синтеза молекул АТФ и повышают жизнеспособность миокарда. Оценка влияния иНГЛТ-2 на маркеры ССЗ показала снижение уровня N-концевого предшественника мозгового натрийуретического пептида и концентрации высокочувствительного тропонина I у пожилых пациентов с сахарным диабетом 2 типа (СД2). Таким образом, описанная группа препаратов оказывает многофакторное воздействие на функционирование сердечно-­сосудистой системы. Дальнейшие исследования помогут расширить спектр благоприятных эффектов иНГЛТ-2 на функцию миокарда как у пациентов с СД2, так и у лиц без нарушений углеводного обмена.

The findings of large-scale cardiovascular outcome trials have been demonstrated that sodium-glucose cotransporter 2 ­inhibitors (iSGLT-2) have shown beneficial cardiovascular effects. In this review proposed mechanisms underlying iSGLT-2-associated cardiovascular benefits have been discussed: haemodynamic and intracellular effects, including metabolic effects and electrolyte changes; and also, the effect on markers of cardiovascular disease (CVD). The hemodynamic effects of SGLT-2 are characterized by reduction of cardiac preload and afterload as a result of osmotic diuresis, a decrease in blood pressure and arterial stiffness. The metabolic effects of this medicine are accompanied by an increase the production of ketone bodies, followed by improving ATP production and myocardial energetics. Also, iSGLT-2 modulate ion transporters (NHE1 and NHE3). A reduction of cytoplasmic sodium and calcium levels and increasing mitochondrial calcium levels in the cardiomyocytes enhances the synthesis of ATP and increases cell viability. Effect of iSGLT-2 on CVD markers showed a decrease in the levels of the N-terminal pro-B-type natriuretic peptide and highly sensitive troponin I in elderly patients with type 2 diabetes mellitus (T2DM). Thus, this class of agents has a multifactorial effect on the functioning of cardiovascular system. Further studies will help to explain the all possible cardioprotective effects of iSGLT-2 in individuals with and without T2DM.

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The authors declare that there are no conflicts of interest present.