actabiomedicaActa Biomedica ScientificaActa Biomedica Scientifica2541-94202587-9596Scientific Centre for Family Health and Human Reproduction Problems10.29413/ABS.2022-7.6.6actabiomedica-3882Research ArticleВНУТРЕННИЕ БОЛЕЗНИINTERNAL DISEASESРоль аргинина и эндотелиальной синтазы оксида азота при заболевании метаболическим синдромом и COVID-19The role of arginine and endothelial nitric oxide synthase in the pathogenesis of Covid-19 complicated by metabolic syndromehttps://orcid.org/0000-0001-9215-6018КузнецоваЛ. А.KuznetsovaL. A.

Кузнецова Людмила Александровна – доктор биологических наук, ведущий научный сотрудник лаборатории молекулярной эндокринологии и нейрохимии 

 194223, г. Санкт-Петербург, пр. Тореза, 44, Россия 

Lyudmila A. Kuznetsova – Dr. Sc. (Biol.), Leading Research Officer at the Laboratory of Molecular Endocrinology and Neurochemistry

Toreza ave. 44, Saint Petersburg 194223,Russian Federation 

praskovia1231@mail.ruhttps://orcid.org/0000-0002-7316-2882БасоваН. Е.BasovaN. E.

Басова Наталия Евгеньевна – кандидат биологических наук, старший научный сотрудник лаборатории молекулярной эндокринологии и нейрохимии 

 194223, г. Санкт-Петербург, пр. Тореза, 44, Россия 

Nataliia E. Basova – Cand. Sc. (Biol.), Senior Research Officer at the Laboratory of Molecular Endocrinology and Neurochemistry

Toreza ave. 44, Saint Petersburg 194223,Russian Federation 

basovnat@mail.ruФГБУН Институт эволюционной физиологии и биохимии им. И.М. Сеченова РАНSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences202229122022765170Copyright © Кузнецова Л.А., Басова Н.Е., 20222022Кузнецова Л.А., Басова Н.Е.Kuznetsova L.A., Basova N.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.actabiomedica.ru/jour/article/view/3882

В данном литературном обзоре представлена роль эндотелиальной синтазы оксида азота (еNO-синтазы) и оксида азота (NO), а также аргинина – субстрата фермента при заболевании метаболическим синдромом и COVID-19 (вирус SARS-CoV-2). Метаболический синдром представляет собой сочетание ожирения, инсулиновой резистентности, гипергликемии, дислипидемии и гипертонии. Показано, что у пожилых людей, пациентов с ожирением, метаболическим синдромом (МС), сахарным диабетом 2-го типа (СД2) и заболевших COVID-19 обнаруживается эндотелиальная дисфункция (ЭД) и активация эндотелия сосудов. ЭД является основной причиной ряда патологических состояний при развитии COVID-19 и ранее у больных МС, при этом выявляется резкое падение уровня оксида азота (NO) за счёт снижения экспрессии и активности еNO-синтазы и рассопряжения фермента, что приводит к нарушению целостности сосудов, то есть к сосудосуживающим, воспалительным и тромбозным состояниям с последующей ишемией органов и отёком тканей. Следует отметить, что МС, СД2, гипертония и ожирение, в частности, являются возрастными заболеваниями, и что с возрастом увеличивается уровень глюкозы крови, снижая биодоступность NO в эндотелиальных клетках. Дефекты метаболизма NO вызывают дисфункцию в лёгочных кровеносных сосудах и ткани лёгких, падает уровень NO, что приводит к нарушениям функции лёгких и коагулопатии. В обзоре приведены возможные механизмы этих нарушений, связанные с ЭД, рассопряжением еNO-синтазы, изменением фосфорилирования и регуляции активности фермента, а также при инсулиновой резистентности. Представлен современный взгляд на роль полиморфизма гена еNO-синтазы в развитии этих патологий. Для повышения уровня эндотелиального NO предлагаются препараты, которые регулируют биодоступность NO. К ним можно отнести аргинин, агонист NO – миноксидил, стероидные гормоны, статины, метформин. Однако необходимы дальнейшие исследования и клинические испытания при разработке стратегий лечения, повышающих уровни NO в эндотелии.

This literature review presents the role of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO), as well as arginine, the enzyme substrate, in the disease of metabolic syndrome and COVID-19 (SARS-CoV-2 virus). Metabolic syndrome is a combination of obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension. It has been shown that in elderly people, patients with obesity, metabolic syndrome, type 2 diabetes mellitus (DM2), and patients with COVID-19, endothelial dysfunction (ED) and vascular endothelial activation are detected. ED is the main cause of a number of pathological conditions during the development of COVID-19 and earlier in patients with metabolic syndrome, while a sharp drop in the level of nitric oxide (NO) is detected due to a decrease in the expression and activity of eNO synthase and enzyme depletion, which leads to a violation of the integrity of bloodvessels, that is, to vasoconstrictive, inflammatory and thrombotic conditions, followed by ischemia of organs and edema of tissues. It should be noted that metabolic syndrome, DM2, hypertension and obesity, in particular, are age-related diseases, and it is known that blood glucose levels increase with age, which reduces the bioavailability of NO in endothelial cells. Defects in the metabolism of NO cause dysfunction in the pulmonary blood vessels, the level of NO decreases, which leads to impaired lung function and coagulopathy. The review presents possible mechanisms of these disorders associated with ED, the release of eNO synthase, changes in phosphorylation and regulation of enzyme activity, as well as insulin resistance. A modern view of the role of the polymorphism of the eNO synthase gene in the development of these pathologies is presented. To increase the level of endothelial NO, drugs are offered that regulate the bioavailability of NO. These include arginine, agonist NO – minoxidil, steroid hormones, statins, metformin. However, further research and clinical trials are needed to develop treatment strategies that increase NO levels in the endothelium.

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