细胞焦亡在腹主动脉瘤中的作用及机制

The role and mechanism of pyroptosis in abdominal aortic aneurysm

腹主动脉瘤是一种与血管壁慢性炎症相关的危及生命的疾病,其具体发病机制尚不完全清楚。近年来越来越多的研究表明,细胞焦亡是一种促炎性程序性细胞死亡,可能在腹主动脉瘤的发生发展中发挥重要作用。本文总结焦亡在腹主动脉瘤进展中的作用,在腹主动脉瘤的临床与基础研究中焦亡相关的NLRP3炎症小体成分和效应介质表达变化,讨论NLRP3炎症小体成分的遗传缺陷或药物抑制对实验性腹主动脉瘤的影响。介绍典型和非典型焦亡通路的机制及其激活和执行过程。讨论几种通过抑制NLRP3炎症小体组装及其效应介质的释放治疗腹主动脉瘤的药物靶点。我们认为细胞焦亡是腹主动脉瘤的一个新的治疗靶点。

Abdominal aortic aneurysm(AAA)is a life-threatening disease associated with chronic inflammation in the vascular wall while its specific pathogenesis is not fully understood.Recently,a growing number of studies have indicated that pyroptosis,which is a pro-inflammatory kind of programmed cell death might play a vital role in AAA.In this review,we first summarize the role of pyroptosis in AAA progression by not only providing a literature review on the expression changes of NLRP3 inflammasome components and effector mediators in clinical and experimental AAAs,but also discussing the effects of genetic defects or pharmacological inhibition of NLRP3 inflammasome components on experimental AAAs.Next,we introduce the mechanism of canonical and non-canonical pathway of pyroptosis and its activation and execution process.Finally,we discuss several pyroptosis-related drug targets for treating AAA by inhibiting the assembly of NLRP3 inflammasome and its effector mediators.In conclusion,we believe that pyroptosis might be a new treatment target of AAA.