First Department of Cardiology, "Hippokration" General Hospital, University of Athens Medical School, 11527 Athens, Greece.
Int J Mol Sci. 2022 Dec 14;23(24):15937. doi: 10.3390/ijms232415937.
Coronary atherosclerosis is a chronic pathological process that involves inflammation together with endothelial dysfunction and lipoprotein dysregulation. Experimental studies during the past decades have established the role of inflammatory cytokines in coronary artery disease, namely interleukins (ILs), tumor necrosis factor (TNF)-α, interferon-γ, and chemokines. Moreover, their value as biomarkers in disease development and progression further enhance the validity of this interaction. Recently, cytokine-targeted treatment approaches have emerged as potential tools in the management of atherosclerotic disease. IL-1β, based on the results of the CANTOS trial, remains the most validated option in reducing the residual cardiovascular risk. Along the same line, colchicine was also proven efficacious in preventing major adverse cardiovascular events in large clinical trials of patients with acute and chronic coronary syndrome. Other commercially available agents targeting IL-6 (tocilizumab), TNF-α (etanercept, adalimumab, infliximab), or IL-1 receptor antagonist (anakinra) have mostly been assessed in the setting of other inflammatory diseases and further testing in atherosclerosis is required. In the future, potential targeting of the NLRP3 inflammasome, anti-inflammatory IL-10, or atherogenic chemokines could represent appealing options, provided that patient safety is proven to be of no concern.
冠状动脉粥样硬化是一种慢性病理过程,涉及炎症以及内皮功能障碍和脂蛋白失调。过去几十年的实验研究已经确定了炎症细胞因子在冠状动脉疾病中的作用,即白细胞介素(ILs)、肿瘤坏死因子(TNF)-α、干扰素-γ和趋化因子。此外,它们作为疾病发展和进展的生物标志物的价值进一步增强了这种相互作用的有效性。最近,针对细胞因子的治疗方法已成为治疗动脉粥样硬化疾病的潜在工具。基于 CANTOS 试验的结果,IL-1β仍然是降低剩余心血管风险的最有效选择。沿着同样的思路,秋水仙碱在预防急性和慢性冠状动脉综合征患者的主要不良心血管事件的大型临床试验中也被证明是有效的。其他针对 IL-6(托珠单抗)、TNF-α(依那西普、阿达木单抗、英夫利昔单抗)或 IL-1 受体拮抗剂(阿那白滞素)的商业上可用的靶向药物主要在其他炎症性疾病的背景下进行了评估,并且需要在动脉粥样硬化中进一步进行测试。在未来,针对 NLRP3 炎性小体、抗炎性 IL-10 或致动脉粥样硬化趋化因子的潜在靶向治疗可能是一种有吸引力的选择,前提是患者安全性不会受到关注。