Атеросклероз: перспективы противовоспалительной терапии
Атеросклероз: перспективы противовоспалительной терапии
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Аннотация
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 ревматического заболевания – ревматоидного артрита. В аспекте участия в патогенезе атеросклеротического поражения сосудов и в качестве перспективной терапевтической «мишени» особый интерес представляет интерлейкин-1β (ИЛ-1β), играющий важную роль в развитии многих острых и хронических иммуновоспалительных заболеваний. Механизмы развития атеросклероза, связанные с ИЛ-1β, определяют способность кристаллов холестерина и других «проатерогенных» факторов индуцировать синтез ИЛ-1β за счет активации NLRP3 инфламмасомы. Убедительные доказательства роли воспаления в развитии атеросклероза в целом и хорошие перспективы противовоспалительной терапии в частности получены в рандомизированном плацебо-контролируемом исследовании CANTOS (Canakinumab Anti-inflammatory Thrombosis Otcomes Study), в котором изучали эффективность лечения моноклональными антителами к ИЛ-1β канакинумабом (Novartis International AG) у больных с тяжелым атеросклеротическим поражением сосудов как нового подхода к вторичной профилактике кардиоваскулярных осложнений. 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.
Ключевые слова: атеросклероз, ревматоидный артрит, цитокины, интерлейкин-1β, канакинумаб, тоцилизумаб.
The contribution of inflammation to the development of atherosclerotic vascular lesions attracts attention to the similarity of the mechanisms of immunopathogenesis of atherosclerosis and classic inflammatory rheumatic disease – rheumatoid arthritis.
In the aspect of participation in the pathogenesis of atherosclerotic vascular lesions and as a promising therapeutic "target" of particular interest is interleukin-1β (IL-1β), which plays an important role in the development of many acute and chronic immunosuppressive diseases.
The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "Pro-atherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome.
The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "proatherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome.
Convincing evidence for the role of inflammation in development of atherosclerosis in General and good prospects of anti-inflammatory therapy in particular obtained in a randomized placebo-controlled study called CANTOS (Canakinumab Anti-inflammatory Thrombosis Otcomes Study), which studied the effectiveness of treatment with monoclonal antibodies to IL-1β canakinumab (Novartis International AG) in patients with severe atherosclerotic vascular lesions as a new approach to secondary prevention of cardiovascular complications.
The results of CАNTOS research, as well as the experience gained in rheumatology in regard to cardiovascular effects of innovative anti-inflammatory drugs, have great importance for the improvement of secondary prevention of atherosclerosis-related cardiovascular complications.
Keywords: atherosclerosis, rheumatoid arthritis, cytokines, interleukin-1β, canakinumab, tocilizumab.
Ключевые слова: атеросклероз, ревматоидный артрит, цитокины, интерлейкин-1β, канакинумаб, тоцилизумаб.
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The contribution of inflammation to the development of atherosclerotic vascular lesions attracts attention to the similarity of the mechanisms of immunopathogenesis of atherosclerosis and classic inflammatory rheumatic disease – rheumatoid arthritis.
In the aspect of participation in the pathogenesis of atherosclerotic vascular lesions and as a promising therapeutic "target" of particular interest is interleukin-1β (IL-1β), which plays an important role in the development of many acute and chronic immunosuppressive diseases.
The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "Pro-atherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome.
The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "proatherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome.
Convincing evidence for the role of inflammation in development of atherosclerosis in General and good prospects of anti-inflammatory therapy in particular obtained in a randomized placebo-controlled study called CANTOS (Canakinumab Anti-inflammatory Thrombosis Otcomes Study), which studied the effectiveness of treatment with monoclonal antibodies to IL-1β canakinumab (Novartis International AG) in patients with severe atherosclerotic vascular lesions as a new approach to secondary prevention of cardiovascular complications.
The results of CАNTOS research, as well as the experience gained in rheumatology in regard to cardiovascular effects of innovative anti-inflammatory drugs, have great importance for the improvement of secondary prevention of atherosclerosis-related cardiovascular complications.
Keywords: atherosclerosis, rheumatoid arthritis, cytokines, interleukin-1β, canakinumab, tocilizumab.
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Авторы
Е.Л. НАСОНОВ 1,2, Т.В. ПОПКОВА 1
1ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», Москва, Россия;
2 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России, кафедра
ревматологии института профессионального образования, Москва, Россия
1 V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia;
2 I.M. Sechenov First Moscow State Medical University, Moscow, Russia
1ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», Москва, Россия;
2 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России, кафедра
ревматологии института профессионального образования, Москва, Россия
________________________________________________
1 V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia;
2 I.M. Sechenov First Moscow State Medical University, Moscow, Russia
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