动脉粥样硬化抗炎治疗的干预靶点探索

Research progress of anti-inflammatory therapy for atherosclerosis

动脉粥样硬化是一种慢性炎性疾病,临床上仍以降低低密度脂蛋白为主要干预靶点,近期几项“后他汀时代”新型降脂药物的临床数据表明,尽管使用了高强度的降脂治疗,仍有大量患者存在“残余炎症风险”。事实上,近年来已有大量临床研究结果表明抗炎治疗可有效降低动脉粥样硬化的临床并发症,但获得令人振奋的结果的同时也发现,直接靶向/阻断炎症可能会导致免疫抑制或感染概率增加。炎症是一个复杂的网络,涉及多种炎性细胞的活化、炎性因子的释放及炎症通路的激活等因素共同参与,因此,寻找有效、安全的抗炎靶点十分必要且意义重大。现有的临床证据表明,靶向先天免疫途径的NOD样受体热蛋白结构域相关蛋白3/白细胞介素-1β/白细胞介素-6/超敏C反应蛋白信号通路是有效的干预靶点,此外,靶向适应性免疫、趋化因子及促炎症消退介质释放等过程亦表现出抗动脉粥样硬化的作用。文中将概述近年来动脉粥样硬化抗炎治疗的最新进展,包括最新的临床研究以及仍处于基础研究阶段的重要进展,展望动脉粥样硬化抗炎治疗的广阔前景。

Atherosclerosis is a chronic inflammatory disease.In clinical practice,the main intervention target is to reduce low density lipoprotein cholesterol.Recent clinical data of several new lipid lowering drugs in the"post statin era"show that despite the use of high-intensity lipid lowering therapy,a large number of patients still have"residual inflammatory risk".In fact,in recent years,a large number of clinical studies have shown that anti-inflammatory treatment can effectively reduce the clinical complications of atherosclerosis,but it is also found that directly targeting/blocking inflammation may lead to increased immunosuppression or infection probability.Inflammation is a complex network involving the activation of multiple inflammatory cells,the release of inflammatory factors and the activation of inflammatory pathways.Therefore,it is necessary and significant to find effective and safe anti-inflammatory targets.Existing clinical evidence shows that targeting NOD-like receptor thermal protein domain associated protein 3/interleukin-1β/interleukin-6/hypersensitive-C-reactive protein pathway is an effective intervention target.In addition,targeted adaptive immunity,chemokines,and the release of proinflammatory regression mediators also show anti atherosclerosis effects.This article will summarize the latest progress in anti-inflammatory treatment of atherosclerosis in recent years,including the latest clinical research and the important progress still in the basic research stage,and look forward to the broad prospects of anti-inflammatory treatment of atherosclerosis.