Molekulyarnaya Meditsina (Molecular medicine)Molekulyarnaya Meditsina (Molecular medicine)Молекулярная медицина1728-29182499-9490Russkiy Vrach Publishing House11338510.29296/24999490-2021-02-02ArticlesСтатьиReview ArticleOn the role of PCSK9 in the development of atherosclerosis: molecular aspectsО роле PCSK9 в развитии атеросклероза: молекулярные аспектыChaulinAleksey MichailovichЧаулинАлексей Михайлович

MD, doctor of clinical laboratory diagnostics, S; postgraduate student, Assistant of the Department of Histology and Embryology

врач клинической лабораторной диагностики клинико-диагностической лаборатории; аспирант, ассистент кафедры гистологии и эмбриологии

alekseymichailovich22976@gmail.comDuplyakovDmitry VictorovichДупляковДмитрий Викторович

PhD, Deputy chief doctor for the medical part; Professor of the Department of Cardiology and Cardiovascular Surgery, professor, doctor of medical sciences

доктор медицинских наук, заместитель главного врача по медицинской части; профессор кафедры кардиологии и сердечно-сосудистой хирургии Института профессионального образования

duplyakov@yahoo.comSamara Regional Cardiological DispensaryГБУЗ «Самарский областной клинический кардиологический диспансер»Samara State Medical UniversityФГБОУ ВО «Самарский государственный медицинский университет» Минздрава России15022021192VOL 19, NO2 (2021)ТОМ 19, №2 (2021)81518112022Copyright ©; 2021, Russkiy Vrach Publishing HouseCopyright ©; 2021, ИД "Русский врач"2021Russkiy Vrach Publishing HouseИД "Русский врач"https://journals.eco-vector.com/1728-2918/article/view/113385

Due to the discovery of the proprotein convertase subtilisin/kexin type 9 (PCSK9) and the establishment of its role in lipoprotein metabolism, it became possible to deliver new groups of effective drugs for the treatment of dyslipidemia. The main function of PCSK9 is to eliminate low-density lipoprotein receptors leading to the development of hypercholesterolemia - one of the key risk factors for atherosclerosis and cardiovascular diseases. Therefore, inhibition of PCSK9 has become a new strategy for hypolipidemic measures. Monoclonal antibodies (class G immunoglobulins) against PCSK9 - alirocumab and evolocumab are currently approved for the use in clinical practice. At the stage of development and clinical trials, there are many additional groups of drugs acting as inhibition of PCSK9 gene expression, PCSK9 matrix RNA translation, and inhibition of the function of the PCSK9 enzyme. This review examines the role of PCSK9 in the regulation of lipoprotein metabolism and describes in detail the molecular mechanisms for regulating the expression of the gene encoding PCSK9. The main groups of new hypolipidemic anti-PCSK9 drugs are also discussed: monoclonal antibodies against PCSK9, small interfering RNAs, antisense nucleotides, small molecules, and the anti-PCSK9 vaccine.

Благодаря открытию пропротеиновой конвертазы субтилизин-кексинового типа 9 (PCSK9) и установлению ее роли в метаболизме липопротеинов появилась возможность создания новых групп эффективных препаратов для терапии дислипидемий. Основная функция PCSK9 состоит в элиминации рецепторов липопротеинов низкой плотности, что приводит к формированию гиперхолестеринемии - одного из ключевых факторов риска атеросклероза и сердечно-сосудистых заболеваний. Поэтому ингибирование PCSK9 стало новой стратегией гиполипидемических мероприятий. Для использования в клинической практике на данный момент одобрены моноклональные антитела (иммуноглобулины класса G) против PCSK9 - алирокумаб и эволокумаб. На этапе разработки и клинических испытаний находятся целый ряд дополнительных групп препаратов, механизм действия которых основан на угнетении экспрессии гена PCSK9, трансляции матричной РНК PCSK9 и ингибировании функции фермента PCSK9. В данном обзоре рассматривается роль PCSK9 в регуляции метаболизма липопротеинов, подробно описываются молекулярные механизмы регуляции экспрессии гена, кодирующего PCSK9. Также обсуждаются основные группы новых гиполипидемических анти-PCS.K9 препаратов: моноклональные антитела против PCSK9, малые интерферирующие РНК, антисмысловые нуклеотиды, малые молекулы, вакцина против PCSK9.

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