- Record: found
- Abstract: found
- Article: found
The cGAS–STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy
review-article
Patrick Kwabena Oduro
a
,
† ,
Xianxian Zheng
a
,
† ,
Jinna Wei
a ,
Yanze Yang
a ,
Yuefei Wang
a
,
b ,
Han Zhang
a
,
b ,
Erwei Liu
a
,
b ,
Xiumei Gao
a
,
b ,
Mei Du
c
,
∗ ,
Qilong Wang
a
,
b
,
∗
20 May 2021
STING,
cGAS,
Cardiovascular diseases,
Metabolic diseases,
Damage-associated molecular patterns,
Inflammation,
ER stress,
Mitochondria,
AA, amino acids,
AAD, aortic aneurysm and dissection,
AKT, protein kinase B,
AMPK, AMP-activated protein kinase,
Ang II, angiotensin II,
ATP, adenosine triphosphate,
CBD, C-binding domain,
CDG, c-di-GMP,
CDNs, cyclic dinucleotides,
cGAMP, 2′,3′-cyclic GMP–AMP,
cGAS, cyclic GMP–AMP synthase,
CTD, C-terminal domain,
CTT, C-terminal tail,
CVDs, cardiovascular diseases,
Cys, cysteine,
DAMPs, danger-associated molecular patterns,
DsbA-L, disulfide-bond A oxidoreductase-like protein,
dsDNA, double-stranded DNA,
ER, endoplasmic reticulum,
GTP, guanosine triphosphate,
HAQ, R71H-G230A-R293Q,
HFD, high-fat diet,
hSTING, human stimulator of interferon genes,
ICAM-1, intracellular adhesion molecule 1,
IFN, interferon,
IFNAR, interferon receptors,
IFN-I, type 1 interferon,
IFNIC, interferon-inducible cells,
IKK, IκB kinase,
IL, interleukin,
IRF3, interferon regulatory factor 3,
ISGs, IRF-3-dependent interferon-stimulated genes,
LBD, ligand-binding pocket,
LPS, lipopolysaccharides,
MI, myocardial infarction,
MLKL, mixed lineage kinase domain-like protein,
MST1, mammalian Ste20-like kinases 1,
mtDNA, mitochondrial DNA,
mTOR, mammalian target of rapamycin,
NAFLD, nonalcoholic fatty liver disease,
NASH, nonalcoholic steatohepatitis,
NF-κB, nuclear factor-kappa B,
NLRP3, NOD-, LRR- and pyrin domain-containing protein 3,
NO2-FA, nitro-fatty acids,
NTase, nucleotidyltransferase,
PDE3B/4, phosphodiesterase-3B/4,
PKA, protein kinase A,
Poly: I.C, polyinosinic-polycytidylic acid,
PPI, protein–protein interface,
ROS, reactive oxygen species,
SAVI, STING-associated vasculopathy with onset in infancy,
Ser, serine,
SNPs, single nucleotide polymorphisms,
STIM1, stromal interaction molecule 1,
STING, stimulator of interferon genes,
TAK1, transforming growth factor β-activated kinase 1,
TBK1, TANK-binding kinase 1,
TFAM, mitochondrial transcription factor A,
TLR, Toll-like receptors,
TM, transmembrane,
TNFα, tumor necrosis factor-alpha,
TRAF6, tumor necrosis factor receptor-associated factor 6,
TREX1, three prime repair exonuclease 1,
YAP1, Yes-associated protein 1
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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.
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Most cited references212
- Record: found
- Abstract: found
- Article: not found
Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.
Zhijian Chen, Lijun Sun, Jiaxi Wu … (2013)
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- Abstract: found
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Regulation of type I interferon responses.
Lionel B Ivashkiv, Laura Donlin (2014)
- Record: found
- Abstract: found
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STING an Endoplasmic Reticulum Adaptor that Facilitates Innate Immune Signaling
Hiroki Ishikawa, Glen N. Barber (2008)
Author and article information
sting,cgas,cardiovascular diseases,metabolic diseases,damage-associated molecular patterns,inflammation,er stress,mitochondria,aa, amino acids,aad, aortic aneurysm and dissection,akt, protein kinase b,ampk, amp-activated protein kinase,ang ii, angiotensin ii,atp, adenosine triphosphate,cbd, c-binding domain,cdg, c-di-gmp,cdns, cyclic dinucleotides,cgamp, 2′,3′-cyclic gmp–amp,cgas, cyclic gmp–amp synthase,ctd, c-terminal domain,ctt, c-terminal tail,cvds, cardiovascular diseases,cys, cysteine,damps, danger-associated molecular patterns,dsba-l, disulfide-bond a oxidoreductase-like protein,dsdna, double-stranded dna,er, endoplasmic reticulum,gtp, guanosine triphosphate,haq, r71h-g230a-r293q,hfd, high-fat diet,hsting, human stimulator of interferon genes,icam-1, intracellular adhesion molecule 1,ifn, interferon,ifnar, interferon receptors,ifn-i, type 1 interferon,ifnic, interferon-inducible cells,ikk, iκb kinase,il, interleukin,irf3, interferon regulatory factor 3,isgs, irf-3-dependent interferon-stimulated genes,lbd, ligand-binding pocket,lps, lipopolysaccharides,mi, myocardial infarction,mlkl, mixed lineage kinase domain-like protein,mst1, mammalian ste20-like kinases 1,mtdna, mitochondrial dna,mtor, mammalian target of rapamycin,nafld, nonalcoholic fatty liver disease,nash, nonalcoholic steatohepatitis,nf-κb, nuclear factor-kappa b,nlrp3, nod-, lrr- and pyrin domain-containing protein 3,no2-fa, nitro-fatty acids,ntase, nucleotidyltransferase,pde3b/4, phosphodiesterase-3b/4,pka, protein kinase a,poly: i.c, polyinosinic-polycytidylic acid,ppi, protein–protein interface,ros, reactive oxygen species,savi, sting-associated vasculopathy with onset in infancy,ser, serine,snps, single nucleotide polymorphisms,stim1, stromal interaction molecule 1,sting, stimulator of interferon genes,tak1, transforming growth factor β-activated kinase 1,tbk1, tank-binding kinase 1,tfam, mitochondrial transcription factor a,tlr, toll-like receptors,tm, transmembrane,tnfα, tumor necrosis factor-alpha,traf6, tumor necrosis factor receptor-associated factor 6,trex1, three prime repair exonuclease 1,yap1, yes-associated protein 1
sting, cgas, cardiovascular diseases, metabolic diseases, damage-associated molecular patterns, inflammation, er stress, mitochondria, aa, amino acids, aad, aortic aneurysm and dissection, akt, protein kinase b, ampk, amp-activated protein kinase, ang ii, angiotensin ii, atp, adenosine triphosphate, cbd, c-binding domain, cdg, c-di-gmp, cdns, cyclic dinucleotides, cgamp, 2′,3′-cyclic gmp–amp, cgas, cyclic gmp–amp synthase, ctd, c-terminal domain, ctt, c-terminal tail, cvds, cardiovascular diseases, cys, cysteine, damps, danger-associated molecular patterns, dsba-l, disulfide-bond a oxidoreductase-like protein, dsdna, double-stranded dna, er, endoplasmic reticulum, gtp, guanosine triphosphate, haq, r71h-g230a-r293q, hfd, high-fat diet, hsting, human stimulator of interferon genes, icam-1, intracellular adhesion molecule 1, ifn, interferon, ifnar, interferon receptors, ifn-i, type 1 interferon, ifnic, interferon-inducible cells, ikk, iκb kinase, il, interleukin, irf3, interferon regulatory factor 3, isgs, irf-3-dependent interferon-stimulated genes, lbd, ligand-binding pocket, lps, lipopolysaccharides, mi, myocardial infarction, mlkl, mixed lineage kinase domain-like protein, mst1, mammalian ste20-like kinases 1, mtdna, mitochondrial dna, mtor, mammalian target of rapamycin, nafld, nonalcoholic fatty liver disease, nash, nonalcoholic steatohepatitis, nf-κb, nuclear factor-kappa b, nlrp3, nod-, lrr- and pyrin domain-containing protein 3, no2-fa, nitro-fatty acids, ntase, nucleotidyltransferase, pde3b/4, phosphodiesterase-3b/4, pka, protein kinase a, poly: i.c, polyinosinic-polycytidylic acid, ppi, protein–protein interface, ros, reactive oxygen species, savi, sting-associated vasculopathy with onset in infancy, ser, serine, snps, single nucleotide polymorphisms, stim1, stromal interaction molecule 1, sting, stimulator of interferon genes, tak1, transforming growth factor β-activated kinase 1, tbk1, tank-binding kinase 1, tfam, mitochondrial transcription factor a, tlr, toll-like receptors, tm, transmembrane, tnfα, tumor necrosis factor-alpha, traf6, tumor necrosis factor receptor-associated factor 6, trex1, three prime repair exonuclease 1, yap1, yes-associated protein 1