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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">rpcardio</journal-id><journal-title-group><journal-title xml:lang="en">Rational Pharmacotherapy in Cardiology</journal-title><trans-title-group xml:lang="ru"><trans-title>Рациональная Фармакотерапия в Кардиологии</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1819-6446</issn><issn pub-type="epub">2225-3653</issn><publisher><publisher-name>«SILICEA-POLIGRAF» LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.20996/1819-6446-2022-12-11</article-id><article-id custom-type="elpub" pub-id-type="custom">rpcardio-2863</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>АКТУАЛЬНЫЕ  ВОПРОСЫ  КЛИНИЧЕСКОЙ ФАРМАКОЛОГИИ</subject></subj-group></article-categories><title-group><article-title>The Pathogenetic Basis of the Action of Bempedoic Acid</article-title><trans-title-group xml:lang="ru"><trans-title>Патогенетические основы эффектов бемпедоевой кислоты</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9194-1302</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Петросян</surname><given-names>А. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Petrosyan</surname><given-names>A. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Петросян Альбина Сергеевна</p><p>Краснодар</p></bio><bio xml:lang="en"><p>Albina S. Petrosyan</p><p>Krasnodar</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8546-3634</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Рудь</surname><given-names>Р. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Rud'</surname><given-names>R. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Рудь Руслан Сергеевич</p><p>Москва</p><p>eLibrary SPIN 3324-0277</p></bio><bio xml:lang="en"><p>Ruslan S. Rud'</p><p>Moscow</p><p>eLibrary SPIN 3324-0277</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9532-0626</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Поляков</surname><given-names>П. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Polyakov</surname><given-names>P. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Поляков Павел Павлович</p><p>Краснодар</p><p>eLibrary SPIN 9349-9545</p></bio><bio xml:lang="en"><p>Pavel P. Polyakov</p><p>Krasnodar</p><p>eLibrary SPIN 9349-9545</p></bio><email xlink:type="simple">palpal.p@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0694-9984</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Каде</surname><given-names>А. Х.</given-names></name><name name-style="western" xml:lang="en"><surname>Kade</surname><given-names>A. Kh.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Каде Азамат Халидович</p><p>Краснодар</p><p>eLibrary SPIN 1415-7612</p></bio><bio xml:lang="en"><p>Azamat Kh. Kade</p><p>Krasnodar</p><p>eLibrary SPIN 1415-7612</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5667-0623</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Занин</surname><given-names>С. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Zanin</surname><given-names>S. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Занин Сергей Александрович</p><p>Краснодар</p><p>eLibrary SPIN 7233-6883</p></bio><bio xml:lang="en"><p>Sergey A. Zanin</p><p>Krasnodar</p><p>eLibrary SPIN 7233-6883</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Кубанский государственный медицинский университет</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Kuban State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>I.M. Sechenov First Moscow State Medical University (Sechenov University)</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>08</day><month>01</month><year>2023</year></pub-date><volume>18</volume><issue>6</issue><fpage>734</fpage><lpage>741</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Petrosyan A.S., Rud' R.S., Polyakov P.P., Kade A.K., Zanin S.A., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Петросян А.С., Рудь Р.С., Поляков П.П., Каде А.Х., Занин С.А.</copyright-holder><copyright-holder xml:lang="en">Petrosyan A.S., Rud' R.S., Polyakov P.P., Kade A.K., Zanin S.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.rpcardio.online/jour/article/view/2863">https://www.rpcardio.online/jour/article/view/2863</self-uri><abstract><p>The modern cardiology has a wide range of medications which affect various pathogenetic links of atherosclerosis, but even the best of them still obtain disadvantages causing intolerance and medicine discontinuation. The development of new hypolipidemic medications will allow not only to introduce alternative therapies into the cardiology practice, but also to completely execute the strategy of residual risk reduction by utilizing rational combinations of medications. One of such alternatives could be bempedoic acid, which can have a positive effect on a number of endpoints as the results of third phase trials have shown. These effects are also confirmed in Mendelian randomization studies. The mechanism of action of bempedoic acid is presumably associated with inhibition of the activity of ATP citrate lyase – the enzyme responsible for the breakdown of citrate into acetyl-CoA and oxaloacetate. Acetyl-CoA, in turn, is used by the cell to synthesize cholesterol and fatty acids. Thus, bempedoic acid affects in the same metabolic pathway as statins, but at an earlier stage. According to this, it is possible that medications of these classes will have similar side effects and pleiotropic effects associated with modulation of the mevalonic pathway, such as prenylation regulatory proteins (small GTPases) or reduction of coenzyme Q synthesis. However, there are also some specific features of the pharmacodynamics and pharmacokinetics of bempedoic acid to be considered. In particular, once entered the body, it must be activated via esterification by very long-chain acyl-CoA synthetase-1. The enzyme isoform required for this process is expressed in a tissue-specific manner and, for example, is absent in skeletal myocytes. In addition, citrate, oxaloacetate, and acetyl-CoA are important regulators of many intracellular processes: metabolism, growth and proliferation, mechanotransduction, posttranslational modifications of histones and other proteins. The levels of all three substances are altered by bempedoic acid, although no firm conclusions about the effects of these changes can be drawn at this time. The mentioned features probably have a significant impact on the clinical profile of bempedoic acid and underlie the differences from statins already observed in third phase trials, including, for example, a reduced risk of the onset or worsening of diabetes mellitus while taking bempedoic acid.</p></abstract><trans-abstract xml:lang="ru"><p>Современная кардиология располагает широким спектром препаратов, воздействующих на различные звенья патогенеза атеросклероза, но даже лучшие из них всё ещё имеют недостатки, которые становятся причиной непереносимости и отмены. Разработка новых гиполипидемических средств позволит не только внедрить в практику кардиолога альтернативные методы лечения, но и максимально полно реализовать стратегию снижения остаточного риска, применяя рациональные комбинации лекарственных средств. Одной из таких альтернатив может стать бемпедоевая кислота, способная, как показали результаты исследований третьей фазы, положительно влиять на ряд конечных точек. Эти эффекты подтверждаются и в работах с использованием менделевской рандомизации. Механизм действия бемпедоевой кислоты связан, предположительно, с подавлением активности АТФ-цитрат-лиазы – фермента, отвечающего за расщепление цитрата на ацетилКоA и оксалоацетат. Ацетил-КоА, в свою очередь, используется клеткой для синтеза холестерина и жирных кислот. Таким образом, бемпедоевая кислота влияет на тот же метаболический путь, что и статины, но на более раннем этапе. Основываясь на этом, можно предположить, что у препаратов этих классов будут обнаружены сходные побочные и плейотропные эффекты, связанные с модуляцией мевалонового пути, например, с пренилированием регуляторных белков (малых ГТФ-аз) или со снижением синтеза коэнзима Q. Однако нельзя забывать и о некоторых особенностях фармакодинамики и фармакокинетики бемпедоевой кислоты. В частности, после поступления в организм она должна быть активирована путем этерификации микросомальной ацил-КоА синтетазой длинноцепочечных жирных кислот 1. Требуемая для этого изоформа фермента экспрессируется тканеспецифично и, например, отсутствует в скелетных миоцитах. Кроме того, цитрат, оксалоацетат и ацетил-КоА являются важными регуляторами многих внутриклеточных процессов: метаболизма, роста и размножения, механотрансдукции, посттрансляционных модификаций гистонов и других белков. Уровень всех трёх веществ изменяется под действием бемпедоевой кислоты, хотя сделать однозначные выводы о последствиях этих изменений на данный момент нельзя. Упомянутые особенности, вероятно, оказывают существенное влияние на клинический профиль бемпедоевой кислоты и лежат в основе уже наблюдаемых в испытаниях третьей фазы отличиях препарата от статинов, среди которых, например, снижение риска возникновения или ухудшения сахарного диабета на фоне приёма бемпедоевой кислоты.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>бемпедоевая кислота</kwd><kwd>АТФ-цитрат-лиаза</kwd><kwd>дислипидемия</kwd><kwd>статины</kwd></kwd-group><kwd-group xml:lang="en"><kwd>bempedoic acid</kwd><kwd>ATP citrate lyase</kwd><kwd>dyslipidemia</kwd><kwd>statins</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Бойцов С.А., Шальнова С.А., Деев А.Д. Эпидемиологическая ситуация как фактор, определяющий стратегию действий по снижению смертности в Российской Федерации. Терапевтический Архив. 2020;92(1):4-9. 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