Rakocevic Jelena, Dobric Milan, Borovic Milica Labudovic, Milutinovic Katarina, Milenkovic Sanela, Tomasevic Miloje
Institute of Histology and Embryology "Aleksandar Đ. Kostić", Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Institute for Cardiovascular Diseases "Dedinje", 11000 Belgrade, Serbia.
Rev Cardiovasc Med. 2023 Jan 4;24(1):10. doi: 10.31083/j.rcm2401010. eCollection 2023 Jan.
Inflammation plays an important role in all stages of atherosclerosis - from endothelial dysfunction, to formation of fatty streaks and atherosclerotic plaque, and its progression to serious complications, such as atherosclerotic plaque rupture. Although dyslipidemia is a key driver of atherosclerosis, pathogenesis of atherosclerosis is now considered interplay between cholesterol and inflammation, with the significant role of the immune system and immune cells. Despite modern therapeutic approaches in primary and secondary cardiovascular prevention, cardiovascular diseases remain the leading cause of mortality worldwide. In order to reduce residual cardiovascular risk, despite the guidelines-guided optimal medical therapy, novel therapeutic strategies are needed for prevention and management of coronary artery disease. One of the innovative and promising approaches in atherosclerotic cardiovascular disease might be inflammation-targeted therapy. Numerous experimental and clinical studies are seeking into metabolic pathways underlying atherosclerosis, in order to find the most suitable pathway and inflammatory marker/s that should be the target for anti-inflammatory therapy. Many anti-inflammatory drugs have been tested, from the well-known broad range anti-inflammatory agents, such as colchicine, allopurinol and methotrexate, to targeted monoclonal antibodies specifically inhibiting a molecule included in inflammatory pathway, such as canakinumab and tocilizumab. To date, there are no approved anti-inflammatory agents specifically indicated for silencing inflammation in patients with coronary artery disease. The most promising results came from the studies which tested colchicine, and studies where the inflammatory-target was NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome/interleukin-1 beta (IL-1 )/interleukin-6 (IL-6)/C-reactive protein (CRP) pathway. A growing body of evidence, along with the ongoing clinical studies, suggest that the anti-inflammatory therapy might become an additional strategy in treating atherosclerotic cardiovascular disease. Herein we present an overview of the role of inflammation in atherosclerosis, the most important inflammatory markers chosen as targets of anti-inflammatory therapy, along with the critical review of the major clinical trials which tested non-targeted and targeted anti-inflammatory drugs in patients with atherosclerotic cardiovascular disease.
炎症在动脉粥样硬化的各个阶段都起着重要作用——从内皮功能障碍到脂肪条纹和动脉粥样硬化斑块的形成，以及其发展为严重并发症，如动脉粥样硬化斑块破裂。尽管血脂异常是动脉粥样硬化的关键驱动因素，但现在认为动脉粥样硬化的发病机制是胆固醇与炎症之间的相互作用，免疫系统和免疫细胞起着重要作用。尽管在一级和二级心血管预防方面有现代治疗方法，但心血管疾病仍然是全球死亡的主要原因。为了降低残余心血管风险，尽管有指南指导的最佳药物治疗，但仍需要新的治疗策略来预防和管理冠状动脉疾病。动脉粥样硬化性心血管疾病中一种创新且有前景的方法可能是炎症靶向治疗。众多实验和临床研究正在探究动脉粥样硬化的代谢途径，以便找到最合适的途径和应作为抗炎治疗靶点的炎症标志物。许多抗炎药物已经过测试，从众所周知的广泛抗炎剂，如秋水仙碱、别嘌醇和甲氨蝶呤，到特异性抑制炎症途径中包含的分子的靶向单克隆抗体，如卡那单抗和托珠单抗。迄今为止，尚无专门批准用于使冠状动脉疾病患者炎症消退的抗炎药物。最有希望的结果来自对秋水仙碱进行测试的研究，以及炎症靶点为含核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎性小体/白细胞介素-1β（IL-1β）/白细胞介素-6（IL-6）/C反应蛋白（CRP）途径的研究。越来越多的证据以及正在进行的临床研究表明，抗炎治疗可能成为治疗动脉粥样硬化性心血管疾病的一种额外策略。在此，我们概述炎症在动脉粥样硬化中的作用、被选为抗炎治疗靶点的最重要炎症标志物，以及对在动脉粥样硬化性心血管疾病患者中测试非靶向和靶向抗炎药物的主要临床试验的批判性综述。
