Роль аргинина и эндотелиальной синтазы оксида азота при заболевании метаболическим синдромом и COVID-19

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.

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