Role of cGAS-STING signaling pathway in cardiometabolic diseases

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Jul 28;48(7):1086-1097. doi: 10.11817/j.issn.1672-7347.2023.230028.
[Article in English, Chinese]

Abstract

Cardiometabolic disease is a common clinical syndrome with exact causal relationship between the aberrant of glucose/lipid metabolism and cardiovascular disfunction, but its pathogenesis is unclear. Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway regulates the activation of innate immunity by sensing intracellular double stranded DNA. Metabolic risk factors drive the activation of cGAS-STING pathway through mitochondrial DNA, nuclear DNA and endoplasmic reticulum stress. In addition, the activation of the cGAS-STING pathway triggers chronic sterile inflammation, excessive activation of autophagy, senescence and apoptosis in related cells of cardiovascular system. These changes induced by cGAS-STING pathway might be implicated in the onset and deterioration of cardiometabolic disease. Therefore, the targeting intervention of cGAS-STING signaling pathway may emerge as a novel treatment for cardiometabolic disease.

代谢性心血管疾病是糖脂代谢紊乱与心血管功能损害之间存在因果关联的临床常见综合征,但具体发病机制不清。环磷酸鸟苷-腺苷酸合成酶(cyclic guanosine monophosphate-adenosine monophosphate synthase,cGAS)-干扰素基因刺激因子(stimulator of interferon gene,STING)信号通路通过识别双链DNA激活固有免疫。代谢性危险因素引起线粒体DNA、核DNA在细胞质中的浓度上升以及内质网应激,驱动cGAS-STING通路激活,从而触发反复无菌性免疫炎症反应、细胞自噬水平上调、细胞衰老及细胞凋亡,最终表现为心血管不良结局的发生与发展。因此,靶向干预cGAS-STING信号通路或将成为治疗代谢性心血管疾病的崭新方式。.

Keywords: autophagy; cardiometabolic disease; cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene signaling pathway; senescence.

MeSH terms

  • Apoptosis
  • Autophagy
  • Cardiovascular Diseases*
  • Glucose
  • Humans
  • Inflammation
  • Signal Transduction*

Substances

  • Glucose