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AIM2炎性小体:心血管疾病中的一种新型生物标志物和靶点。

The AIM2 inflammasome: A novel biomarker and target in cardiovascular disease.

作者信息

Du Luping, Wang Xuyang, Chen Siyuan, Guo Xiaogang

机构信息

Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

出版信息

Pharmacol Res. 2022 Dec;186:106533. doi: 10.1016/j.phrs.2022.106533. Epub 2022 Nov 2.

Abstract

Absent in melanoma 2 (AIM2) is a cytoplasmic sensor that recognises the double-strand DNA. AIM2 inflammasome is a protein platform in the cell that initiates innate immune responses by cleaving pro-caspase-1 and converting IL-1β and IL-18 to their mature forms. Additionally, AIM2 inflammasome promotes pyroptosis by converting Gasdermin-D (GSDMD) to GSDMD-N fragments. An increasing number of studies have indicated the important and decisive roles of the AIM2 inflammasome, IL-1β, and pyroptosis in cardiovascular diseases, such as coronary atherosclerosis, myocardial infarction, ischaemia/reperfusion injury, heart failure, aortic aneurysm and ischaemic stroke. Here, we review the molecular mechanism of the activation and effect of the AIM2 inflammasome in cardiovascular disease, revealing new insights into pathogenic factors that may be targeted to treat cardiovascular disease and related dysfunctions.

摘要

黑色素瘤缺乏因子2(AIM2)是一种识别双链DNA的胞质传感器。AIM2炎性小体是细胞内的一个蛋白质平台,通过切割前半胱天冬酶-1并将白细胞介素-1β(IL-1β)和白细胞介素-18转化为成熟形式来启动先天免疫反应。此外,AIM2炎性小体通过将gasdermin-D(GSDMD)转化为GSDMD-N片段来促进细胞焦亡。越来越多的研究表明,AIM2炎性小体、IL-1β和细胞焦亡在心血管疾病中发挥着重要且决定性的作用,如冠状动脉粥样硬化、心肌梗死、缺血/再灌注损伤、心力衰竭、主动脉瘤和缺血性中风。在此,我们综述了AIM2炎性小体在心血管疾病中的激活分子机制及其作用,揭示了可能成为治疗心血管疾病及相关功能障碍靶点的致病因素的新见解。

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