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无菌性炎症与心血管疾病之间的联系:聚焦cGAS-STING通路在发病机制及治疗前景中的作用

Link between sterile inflammation and cardiovascular diseases: Focus on cGAS-STING pathway in the pathogenesis and therapeutic prospect.

作者信息

Du Yao, Zhang Hui, Nie Xiaoyan, Qi Yajun, Shi Shi, Han Yingying, Zhou Wenchen, He Chaoyong, Wang Lintao

机构信息

Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Department of Stomatology, Children's Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Front Cardiovasc Med. 2022 Aug 22;9:965726. doi: 10.3389/fcvm.2022.965726. eCollection 2022.

Abstract

Sterile inflammation characterized by unresolved chronic inflammation is well established to promote the progression of multiple autoimmune diseases, metabolic disorders, neurodegenerative diseases, and cardiovascular diseases, collectively termed as sterile inflammatory diseases. In recent years, substantial evidence has revealed that the inflammatory response is closely related to cardiovascular diseases. Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway which is activated by cytoplasmic DNA promotes the activation of interferon regulatory factor 3 (IRF3) or nuclear factor-κB (NF-κB), thus leading to upregulation of the levels of inflammatory factors and interferons (IFNs). Therefore, studying the role of inflammation caused by cGAS-STING pathway in cardiovascular diseases could provide a new therapeutic target for cardiovascular diseases. This review focuses on that cGAS-STING-mediated inflammatory response in the progression of cardiovascular diseases and the prospects of cGAS or STING inhibitors for treatment of cardiovascular diseases.

摘要

以未解决的慢性炎症为特征的无菌性炎症已被充分证实可促进多种自身免疫性疾病、代谢紊乱、神经退行性疾病和心血管疾病的进展,这些疾病统称为无菌性炎症性疾病。近年来,大量证据表明炎症反应与心血管疾病密切相关。由细胞质DNA激活的环磷酸鸟苷-磷酸腺苷合成酶(cGAS)-干扰素基因刺激物(STING)途径促进干扰素调节因子3(IRF3)或核因子-κB(NF-κB)的激活,从而导致炎症因子和干扰素(IFN)水平上调。因此,研究cGAS-STING途径引起的炎症在心血管疾病中的作用可为心血管疾病提供新的治疗靶点。本综述重点关注cGAS-STING介导的炎症反应在心血管疾病进展中的作用以及cGAS或STING抑制剂治疗心血管疾病的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a3e/9441773/f62e60bbf0bb/fcvm-09-965726-g0001.jpg

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