Atherosclerosis is considered a chronic, inflammatory disease responsible for more than 15% of all global deaths, secondary to its complications of myocardial infarction, vascular disease, and stroke. Current treatment regimens consist of lipid-lowering pharmaceuticals, control of risk factors, and prevention of plaque rupture and thrombosis with antiplatelet agents. However, a significant burden on society remains due to the morbidity and mortality of coronary artery disease despite our best practices. In addition to dyslipidemia and hemostasis, inflammation has now moved to the proverbial forefront as the remaining obstacle to appropriate management of atherosclerosis. A complex dance of endothelial dysfunction, complement activation, and immune cell-mediated cytokine release underlie the pathogenesis of atherosclerotic plaque development, destabilization, and rupture. Cholesterol-induced sterile inflammation is thought to be central to this process via activation of a protein complex called the nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome. The focus of this review article will be to examine the NLRP3 inflammasome, which directs the release of interleukin-1, leading to downstream pro-inflammatory effects, and its potential for therapeutic targeting using currently available and future tools in our pharmacologic arsenal. In particular, we focus on the results of several large, recently concluded clinical trials including the Canakinumab Antiinflammatory Thrombosis Outcome Study, Colchicine Cardiovascular Outcomes Trial, and the Low-Dose Colchicine Study, examining the efficacy of direct inhibition of interleukin-1 with canakinumab or a multimodal approach to inhibiting the NLRP3 inflammasome using colchicine, as well as an overview of novel small molecule inhibitors that are still in development.

动脉粥样硬化被认为​​是一种慢性炎症性疾病，占全球死亡人数的 15% 以上，继发于心肌梗死、血管疾病和中风等并发症。目前的治疗方案包括降脂药物、控制危险因素以及用抗血小板药物预防斑块破裂和血栓形成。然而，尽管我们采取了最佳做法，但冠状动脉疾病的发病率和死亡率仍然给社会带来重大负担。除了血脂异常和止血之外，炎症现在已成为众所周知的动脉粥样硬化适当治疗的剩余障碍。内皮功能障碍、补体激活和免疫细胞介导的细胞因子释放的复杂过程是动脉粥样硬化斑块发展、不稳定和破裂的发病机制的基础。胆固醇诱导的无菌炎症被认为是这一过程的核心，它通过激活一种蛋白质复合物（称为核苷酸结合寡聚化结构域、富含亮氨酸重复序列和含有吡啶结构域的 3 (NLRP3) 炎症小体）来实现。这篇综述文章的重点是检查 NLRP3 炎性小体，它引导白细胞介素-1的释放，导致下游促炎作用，及其使用我们药理学库中当前可用和未来工具进行治疗靶向的潜力。我们特别关注最近结束的几项大型临床试验的结果，包括卡那奴单抗抗炎血栓形成结果研究、秋水仙碱心血管结果试验和低剂量秋水仙碱研究，检查用卡那奴单抗或卡那奴单抗直接抑制白细胞介素-1的功效。使用秋水仙碱抑制 NLRP3 炎症小体的多模式方法，以及仍在开发中的新型小分子抑制剂的概述。