Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Cardiovasc Res. 2022 Jan 29;118(2):372-385. doi: 10.1093/cvr/cvab010.
Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) is an intracellular innate immune receptor that recognizes a diverse range of stimuli derived from pathogens, damaged or dead cells, and irritants. NLRP3 activation causes the assembly of a large multiprotein complex termed the NLRP3 inflammasome, and leads to the secretion of bioactive interleukin (IL)-1β and IL-18 as well as the induction of inflammatory cell death termed pyroptosis. Accumulating evidence indicates that NLRP3 inflammasome plays a key role in the pathogenesis of sterile inflammatory diseases, including atherosclerosis and other vascular diseases. Indeed, the results of the Canakinumab Anti-inflammatory Thrombosis Outcome Study trial demonstrated that IL-1β-mediated inflammation plays an important role in atherothrombotic events and suggested that NLRP3 inflammasome is a key driver of atherosclerosis. In this review, we will summarize the current state of knowledge regarding the role of NLRP3 inflammasome in vascular diseases, in particular in atherosclerosis, vascular injury, aortic aneurysm, and Kawasaki disease vasculitis, and discuss NLRP3 inflammasome as a therapeutic target for these disorders.
核苷酸结合寡聚化结构域样受体家族富含 pyrin 结构域蛋白 3（NLRP3）是一种细胞内先天免疫受体，可识别来自病原体、受损或死亡细胞以及刺激物的多种刺激。NLRP3 的激活导致称为 NLRP3 炎性体的大型多蛋白复合物的组装，并导致生物活性白细胞介素（IL）-1β和 IL-18 的分泌以及称为细胞焦亡的炎症细胞死亡的诱导。越来越多的证据表明，NLRP3 炎性体在无菌性炎症性疾病的发病机制中起关键作用，包括动脉粥样硬化和其他血管疾病。事实上，Canakinumab 抗炎性血栓形成结局研究试验的结果表明，IL-1β 介导的炎症在动脉粥样硬化血栓形成事件中起重要作用，并提示 NLRP3 炎性体是动脉粥样硬化的关键驱动因素。在这篇综述中，我们将总结 NLRP3 炎性体在血管疾病，特别是在动脉粥样硬化、血管损伤、腹主动脉瘤和川崎病血管炎中的作用的最新知识，并讨论 NLRP3 炎性体作为这些疾病的治疗靶点。
