1. The cGAS–STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy
- Author
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Qilong Wang, Yanze Yang, Mei Du, Jinna Wei, Xianxian Zheng, Zhang Han, Erwei Liu, Xiumei Gao, Yuefei Wang, and Patrick Kwabena Oduro
- Subjects
HFD, high-fat diet ,Cys, cysteine ,cGAS, cyclic GMP–AMP synthase ,Review ,Poly: I.C, polyinosinic-polycytidylic acid ,SAVI, STING-associated vasculopathy with onset in infancy ,Bioinformatics ,PPI, protein–protein interface ,TRAF6, tumor necrosis factor receptor-associated factor 6 ,TREX1, three prime repair exonuclease 1 ,STIM1, stromal interaction molecule 1 ,0302 clinical medicine ,AA, amino acids ,GTP, guanosine triphosphate ,MLKL, mixed lineage kinase domain-like protein ,ICAM-1, intracellular adhesion molecule 1 ,Medicine ,PDE3B/4, phosphodiesterase-3B/4 ,General Pharmacology, Toxicology and Pharmaceutics ,IKK, IκB kinase ,NF-κB, nuclear factor-kappa B ,cGAMP, 2′,3′-cyclic GMP–AMP ,NLRP3, NOD-, LRR- and pyrin domain-containing protein 3 ,0303 health sciences ,dsDNA, double-stranded DNA ,TFAM, mitochondrial transcription factor A ,Fatty liver ,Damage-associated molecular patterns ,IFNIC, interferon-inducible cells ,CTD, C-terminal domain ,Mitochondria ,Crosstalk (biology) ,Cardiovascular diseases ,SNPs, single nucleotide polymorphisms ,030220 oncology & carcinogenesis ,Stimulator of interferon genes ,AAD, aortic aneurysm and dissection ,MI, myocardial infarction ,IFNAR, interferon receptors ,ER stress ,CVDs, cardiovascular diseases ,NASH, nonalcoholic steatohepatitis ,Intracellular ,CDG, c-di-GMP ,NTase, nucleotidyltransferase ,ATP, adenosine triphosphate ,Ser, serine ,mTOR, mammalian target of rapamycin ,RM1-950 ,STING, stimulator of interferon genes ,hSTING, human stimulator of interferon genes ,AKT, protein kinase B ,CDNs, cyclic dinucleotides ,TLR, Toll-like receptors ,ER, endoplasmic reticulum ,03 medical and health sciences ,LBD, ligand-binding pocket ,ROS, reactive oxygen species ,YAP1, Yes-associated protein 1 ,IFN, interferon ,ISGs, IRF-3-dependent interferon-stimulated genes ,DAMPs, danger-associated molecular patterns ,IFN-I, type 1 interferon ,030304 developmental biology ,Inflammation ,Ang II, angiotensin II ,TNFα, tumor necrosis factor-alpha ,business.industry ,IRF3, interferon regulatory factor 3 ,CTT, C-terminal tail ,Autophagy ,TAK1, transforming growth factor β-activated kinase 1 ,Metabolic diseases ,medicine.disease ,HAQ, R71H-G230A-R293Q ,IL, interleukin ,mtDNA, mitochondrial DNA ,AMPK, AMP-activated protein kinase ,Sting ,Apoptosis ,TBK1, TANK-binding kinase 1 ,CBD, C-binding domain ,LPS, lipopolysaccharides ,NO2-FA, nitro-fatty acids ,PKA, protein kinase A ,NAFLD, nonalcoholic fatty liver disease ,Therapeutics. Pharmacology ,DsbA-L, disulfide-bond A oxidoreductase-like protein ,business ,Homeostasis ,MST1, mammalian Ste20-like kinases 1 ,TM, transmembrane ,STING ,cGAS - Abstract
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., Graphical abstract 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.Image 1
- Published
- 2022