Противовоспалительная терапия атеросклероза - вклад и уроки ревматологии
Автор: Насонов Е.Л., Попкова Т.В.
Журнал: Научно-практическая ревматология @journal-rsp
Рубрика: Передовая
Статья в выпуске: 5 т.55, 2017 года.
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По современным представлениям, хроническое субклиническое (low grade) воспаление, развитие которого связывают с неконтролируемой активацией как врожденного, так и приобретенного иммунитета, играет фундаментальную роль на всех стадиях атеросклеротического процесса. Вклад воспаления в развитие атеросклеротического поражения сосудов привлекает внимание к схожести механизмов иммунопатогенеза атеросклероза и классического иммуновоспалительного заболевания (ИВЗ) - ревматоидного артрита (РА). В аспекте участия в патогенезе атеросклеротического поражения сосудов и в качестве перспективной терапевтической «мишени» особый интерес представляет интерлейкин 1β (ИЛ1β), играющий важную роль в развитии многих острых и хронических ИВЗ. Механизмы развития атеросклероза, связанные с ИЛ1β, определяют способность кристаллов холестерина (ХС) и других «проатерогенных» факторов индуцировать синтез ИЛ1β за счет активации NLRP3-инфламмасомы. Веские доказательства роли воспаления в развитии атеросклероза, в целом, и хорошие перспективы противовоспалительной терапии, в частности, получены в рандомизированном плацебоконтролируемом исследовании (РПКИ) CANTOS (Canakinumab ANti-inflammatory Thrombosis Otcomes Study), посвященном изучению эффективности лечения моноклональными антителами к ИЛ1β канакинумабом (Novartis International AG) больных с тяжелым атеросклеротическим поражением сосудов как нового подхода к вторичной профилактике кардиоваскулярных осложнений. В настоящее время убедительно показано, что метотрексат (МТ) - эффективный препарат («золотой стандарт») в отношении не только контроля воспалительной активности РА, но и существенного снижения риска кардиоваскулярных катастроф. Это послужило основанием для планирования РПКИ CIRT (The Cardiovascular Inflammation Reduction Trial) с целью оценить антиатерогенный эффект МТ в общей популяции пациентов, страдающих ишемической болезнью сердца. Результаты исследования CANTOS, а также опыт, накопленный в ревматологии в отношении кардиоваскулярных эффектов инновационных противовоспалительных препаратов, имеют огромное значение для совершенствования вторичной профилактики связанных с атеросклерозом кардиоваскулярных осложнений.
Атеросклероз, ревматоидный артрит, цитокины, интерлейкин 1ß, канакинумаб, метотрексат
Короткий адрес: https://sciup.org/14945849
IDR: 14945849 | DOI: 10.14412/1995-4484-2017-465-473
Anti-inflammatory therapy for atherosclerosis: contribution to and lessons of rheumatology
According to modern views, chronic low-grade inflammation, the development of which is associated with the uncontrolled activation of both innate and acquired immunity, plays a fundamental role at all stages of the atherosclerotic process. The contribution of inflammation to the development of an atherosclerotic vascular lesion drew attention to the similarity of the mechanisms in the immunopathogenesis of atherosclerosis and the classic immunoinflammatory disease (IID) - rheumatoid arthritis (RA). Interleukin 1ß (IL-1ß), which plays an important role in the development of many acute and chronic IIDs, is of particular interest with regard to its implication in the pathogenesis of an atherosclerotic vascular lesion and as a promising therapeutic target. The atherosclerosis development mechanisms related to IL-1ß determine the ability of cholesterol crystals and other proatherogenic factors to induce IL-1 ß synthesis due to NLRP3 inflammasome activation. There is strong evidence that inflammation plays a role in the development of atherosclerosis as a whole and that anti-inflammatory therapy has good prospects particularly in the randomized placebo-controlled trial (RPCT) CANTOS (Canakinumab ANti-inflammatory Thrombosis Outcomes Study) investigating the efficiency of treatment with canakinumab (Novartis International AG), an anti-IL-1ß monoclonal antibodies, in patients with severe atherosclerotic vascular lesions as a new approach to secondary prevention of cardiovascular events. Methotrexate (MTX) has now been convincingly shown to be an effective drug (a gold standard) in not only controlling the inflammatory activity of RA, but also in significantly reducing the risks of cardiovascular catastrophes. This has served as a basis for planning the RPCT CIRT (The Cardiovascular Inflammation Reduction Trial) to evaluate the antiatherogenic effect of MTX in the general population of patients with coronary heart disease. The CANTOS results and the experience gained in rheumatology to determine the cardiovascular effects of innovative anti-inflammatory drugs are of great importance in improving the secondary prevention of atherosclerosis-related cardiovascular events.
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