The cGAS-STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy.
The cGAS-STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy.
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心血管和代谢疾病中的cGAS-STING信号：未来药物治疗的新靶点选择
DOI：
10.1016/j.apsb.2021.05.011
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Oduro PK;Zheng X;Wei J;Yang Y;Wang Y;Zhang H;Liu E;Gao X;Du M;Wang Q
干扰素基因（STING）信号传导的环GMP-AMP合酶（cGAS）刺激因子通过诱导细胞因子（主要是I型干扰素）在微生物和肿瘤免疫学中发挥重要的调节功能。近年来，cGAS-STING轴的异常和紊乱的信号传导与多种无菌炎症性疾病密切相关，包括心力衰竭、心肌梗死、心脏肥大、非酒精性脂肪肝、主动脉瘤和夹层、肥胖等。（线粒体DNA，细胞外囊泡中的DNA）从对代谢细胞器和组织的复发性损伤中释放，其由该途径感测。此外，cGAS-STING途径与细胞内基本稳态过程如凋亡、自噬交叉，并调节细胞代谢。靶向脱轨的STING信号传导已成为慢性炎症性疾病的必要条件。同时，过量的I型干扰素信号对心血管和代谢健康的影响仍然完全难以捉摸。在这篇综述中，我们总结了cGAS-STING通路与心血管和代谢疾病之间的密切联系。我们还讨论了一些潜在的小分子抑制剂的途径。这篇综述提供了洞察力，以激发兴趣，并支持未来的研究，了解心血管和代谢组织和疾病的信号轴。综述总结了cGAS-STING信号过度激活的当前影响，重点是与心血管和代谢疾病的联系以及新兴途径的抑制剂的治疗前景。
The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS–STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS–STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS–STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases. The review summarizes the current impact of hyperactivation of the cGAS–STING signaling, with emphasis on the link with cardiovascular and metabolic diseases and the emerged pathway's inhibitors for therapeutic prospects.
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