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动脉粥样硬化:抗炎治疗的前景

Atherosclerosis: perspectives of anti-inflammatory therapy.

作者信息

Nasonov E L, Popkova T V

机构信息

V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia.

I.M. Sechenov First Moscow State Medical University, Moscow, Russia.

出版信息

Ter Arkh. 2018 May 11;90(5):4-12. doi: 10.26442/terarkh201890514-12.

Abstract

According to modern ideas, chronic low-grade inflammation, which development is associated with uncontrolled activation of both innate and adaptive immunity, plays a fundamental role in all stages of the atherosclerotic process. 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.

摘要

根据现代观点,慢性低度炎症在动脉粥样硬化过程的各个阶段都起着基础性作用,其发展与固有免疫和适应性免疫的失控激活相关。炎症在动脉粥样硬化性血管病变发展中的作用,引发了人们对动脉粥样硬化免疫发病机制与经典炎症性风湿疾病——类风湿关节炎之间相似性的关注。在参与动脉粥样硬化性血管病变发病机制方面,特别受关注且有前景的治疗“靶点”是白细胞介素-1β(IL-1β),它在许多急慢性免疫抑制疾病的发展中起重要作用。与IL-1β相关的动脉粥样硬化机制决定了胆固醇晶体和其他“促动脉粥样硬化”因子通过激活NLRP3炎性小体诱导IL-1β合成的能力。与IL-1β相关的动脉粥样硬化机制决定了胆固醇晶体和其他“促动脉粥样硬化”因子通过激活NLRP3炎性小体诱导IL-1β合成的能力。在一项名为CANTOS(卡那单抗抗炎血栓形成结果研究)的随机安慰剂对照研究中,获得了炎症在动脉粥样硬化总体发展中作用的令人信服的证据,以及抗炎治疗尤其是良好前景的证据。该研究探讨了用抗IL-1β单克隆抗体卡那单抗(诺华国际公司)治疗严重动脉粥样硬化性血管病变患者作为心血管并发症二级预防新方法的有效性。CANTOS研究结果以及在风湿病学中关于创新抗炎药物心血管效应所获得的经验,对于改善动脉粥样硬化相关心血管并发症的二级预防具有重要意义。

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