潜质未定克隆性造血致动脉粥样硬化及NLRP3炎性小体治疗作用研究进展

Research progress on atherosclerosis induced by clonal hematopoiesis of indeterminate potential and the therapeutic effect of NLRP3 inflammasome

近年来有研究显示,体细胞驱动基因突变导致的潜质未定克隆性造血(CHIP)刺激炎症标志物升高是动脉粥样硬化性心血管疾病发生及发展的因素之一,核苷酸结合寡聚结构域样受体家族Pyrin结构域中的NLRP3炎性小体,是细胞焦亡的重要调控分子,在其炎症过程中起着关键作用。MCC950作为一种特定的小分子抑制剂,对于NLRP3炎性小体介导细胞焦亡具有选择性的抑制作用,因此,MCC950有望成为临床治疗CHIP介导炎症所致动脉粥样硬化性心血管疾病的有效药物。本文从CHIP相关基因突变入手,概述了NLRP3炎性小体调控细胞焦亡作用于动脉粥样硬化发病机制,以及NLRP3炎性小体选择性抑制剂MCC950作用于CHIP诱发动脉粥样硬化的作用及机制,为临床治疗动脉粥样硬化开辟新的道路。

In recent years,some studies have shown that the increase of inflammatory markers,which results from the clonal hematopoiesis of indeterminate potential(CHIP)caused by somatic cell driven gene mutation,is one of the factors for the occurrence and development of atherosclerotic cardiovascular disease.The NLRP3 inflammasome in the Pyrin domain of the nucleotide-binding oligomeric domain-like receptor family,is an important regulator of pyroptosis and plays a key role in the inflammatory process.As a specific small-molecule inhibitor,MCC950 has a selective inhibitory effect on NLRP3 inflammasome mediated pyroptosis.Therefore,MCC950 is expected to become an effective drug for the clinical treatment of atherosclerotic cardiovascular diseases caused by inflammation mediated by CHIP.Starting from the related mutation of CHIP induced gene,this paper summarizes the pathogenesis of atherosclerosis mediated by the regulation of pyroptosis by NLRP3 inflammasome,and the role and mechanism of selective inhibitor MCC950 of NLRP3 inflammasome on the induction of atherosclerosis by CHIP,so as to provide a basis for clinical treatment of atherosclerosis.