干扰素基因(STING)信号的环GMP-AMP合酶(cGAS)-刺激物通过诱导细胞因子在微生物和肿瘤免疫学中发挥重要的调节功能,主要是I型干扰素。最近,cGAS-STING轴的异常和紊乱信号与多种无菌性炎症性疾病密切相关,包括心力衰竭,心肌梗塞,心脏肥大,非酒精性脂肪性肝病,主动脉瘤和夹层,肥胖,等。这是因为大量的损伤相关分子模式(线粒体DNA,细胞外囊泡中的DNA)从代谢细胞器和组织的复发性损伤中释放,这是由路径感知。此外,cGAS-STING通路与细胞内基本稳态过程如细胞凋亡的串扰,自噬,调节细胞代谢.靶向脱轨的STING信号已经成为慢性炎性疾病所必需的。同时,过度的I型干扰素信号传导对心血管和代谢健康的影响仍然难以捉摸.在这次审查中,我们总结了cGAS-STING通路与心血管和代谢紊乱之间的密切联系。我们还讨论了该途径的一些潜在小分子抑制剂。这篇综述提供了见解,以激发人们对心血管和代谢组织和疾病中这种信号轴的兴趣并支持未来的研究。
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.