The cGAS-STING Pathway: A Ubiquitous Checkpoint Perturbing Myocardial Attributes

Page: [152 - 162] Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

As an innate immune route of defense against microbial infringement, cyclic guanosine monophosphate (GMP)–adenosine monophosphate (AMP) synthase (cGAS)- stimulator of interferon genes (STING) signaling does not simply participate in amplifying inflammatory responses via releasing type-I interferon (IFN) or enhance the expression of pro-inflammatory genes, but also interplays with multifarious pathophysiological activities, such as autophagy, apoptosis, pyroptosis, ferroptosis, and senescence in a broad repertoire of cells like endothelial cells, macrophages and cardiomyocyte. Thus, the cGAS-STING pathway is closely linked with aberrant heart morphologically and functionally via these mechanisms. The past few decades have witnessed an increased interest in the exact relationship between the activation of the cGAS-STING pathway and the initiation or development of certain cardiovascular diseases (CVD). A group of scholars has gradually investigated the perturbation of myocardium affected by the overactivation or suppression of the cGAS-STING. This review focuses on how the cGAS-STING pathway interweaves with other pathways and creates a pattern of dysfunction associated with cardiac muscle. This sets treatments targeting the cGAS-STING pathway apart from traditional therapeutics for cardiomyopathy and achieves better clinical value.

Graphical Abstract

[1]
Rech L, Rainer PP. The innate immune cGAS-STING-pathway in cardiovascular diseases – A mini review. Front Cardiovasc Med 2021; 8: 715903.
[http://dx.doi.org/10.3389/fcvm.2021.715903] [PMID: 34381828]
[2]
Khalifa AA, El Sokkary NH, Elblehi SS, Diab MA, Ali MA. Potential cardioprotective effect of octreotide via NOXs mitigation, mitochondrial biogenesis and MAPK/Erk1/2/STAT3/NF-kβ pathway attenuation in isoproterenol-induced myocardial infarction in rats. Eur J Pharmacol 2022; 925: 174978.
[http://dx.doi.org/10.1016/j.ejphar.2022.174978] [PMID: 35500641]
[3]
Li D, Pi W, Sun Z, Liu X, Jiang J. Ferroptosis and its role in cardiomyopathy. Biomed Pharmacother 2022; 153: 113279.
[http://dx.doi.org/10.1016/j.biopha.2022.113279] [PMID: 35738177]
[4]
Wu X, Li Y, Zhang S, Zhou X. Ferroptosis as a novel therapeutic target for cardiovascular disease. Theranostics 2021; 11(7): 3052-9.
[http://dx.doi.org/10.7150/thno.54113] [PMID: 33537073]
[5]
Yan M, Li Y, Luo Q, et al. Mitochondrial damage and activation of the cytosolic DNA sensor cGAS–STING pathway lead to cardiac pyroptosis and hypertrophy in diabetic cardiomyopathy mice. Cell Death Discov 2022; 8(1): 258.
[http://dx.doi.org/10.1038/s41420-022-01046-w] [PMID: 35538059]
[6]
Fang X, Wang H, Han D, et al. Ferroptosis as a target for protection against cardiomyopathy. Proc Natl Acad Sci 2019; 116(7): 2672-80.
[http://dx.doi.org/10.1073/pnas.1821022116] [PMID: 30692261]
[7]
Wu NN, Zhang Y, Ren J. Mitophagy, mitochondrial dynamics, and homeostasis in cardiovascular aging. Oxid Med Cell Longev 2019; 2019: 1-15.
[http://dx.doi.org/10.1155/2019/9825061] [PMID: 31781358]
[8]
Tocchi A, Quarles EK, Basisty N, Gitari L, Rabinovitch PS. Mitochondrial dysfunction in cardiac aging. Biochim Biophys Acta Bioenerg 2015; 1847(11): 1424-33.
[http://dx.doi.org/10.1016/j.bbabio.2015.07.009] [PMID: 26191650]
[9]
Li T, Chen ZJ. The cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer. J Exp Med 2018; 215(5): 1287-99.
[http://dx.doi.org/10.1084/jem.20180139] [PMID: 29622565]
[10]
Quan Y, Xin Y, Tian G, Zhou J, Liu X. Mitochondrial ROS-modulated mtDNA: A potential target for cardiac aging. Oxid Med Cell Longev 2020; 2020: 1-11.
[http://dx.doi.org/10.1155/2020/9423593] [PMID: 32308810]
[11]
Pham PT, Fukuda D, Nishimoto S, et al. STING, a cytosolic DNA sensor, plays a critical role in atherogenesis: a link between innate immunity and chronic inflammation caused by lifestyle-related diseases. Eur Heart J 2021; 42(42): 4336-48.
[http://dx.doi.org/10.1093/eurheartj/ehab249] [PMID: 34226923]
[12]
Cinat D, Coppes RP, Barazzuol L. DNA damage-induced inflammatory microenvironment and adult stem cell response. Front Cell Dev Biol 2021; 9: 729136.
[http://dx.doi.org/10.3389/fcell.2021.729136] [PMID: 34692684]
[13]
Decout A, Katz JD, Venkatraman S, Ablasser A. The cGAS–STING pathway as a therapeutic target in inflammatory diseases. Nat Rev Immunol 2021; 21(9): 548-69.
[http://dx.doi.org/10.1038/s41577-021-00524-z] [PMID: 33833439]
[14]
Loo TM, Miyata K, Tanaka Y, Takahashi A. Cellular senescence and senescence‐associated secretory phenotype via the cGAS‐STING signaling pathway in cancer. Cancer Sci 2020; 111(2): 304-11.
[http://dx.doi.org/10.1111/cas.14266] [PMID: 31799772]
[15]
Wang S, Wang L, Qin X, et al. ALDH2 contributes to melatonin-induced protection against APP/PS1 mutation-prompted cardiac anomalies through cGAS-STING-TBK1-mediated regulation of mitophagy. Signal Transduct Target Ther 2020; 5(1): 119.
[http://dx.doi.org/10.1038/s41392-020-0171-5] [PMID: 32703954]
[16]
Gui X, Yang H, Li T, et al. Autophagy induction via STING trafficking is a primordial function of the cGAS pathway. Nature 2019; 567(7747): 262-6.
[http://dx.doi.org/10.1038/s41586-019-1006-9] [PMID: 30842662]
[17]
Ding R, Li H, Liu Y, et al. Activating cGAS–STING axis contributes to neuroinflammation in CVST mouse model and induces inflammasome activation and microglia pyroptosis. J Neuroinflammation 2022; 19(1): 137.
[http://dx.doi.org/10.1186/s12974-022-02511-0] [PMID: 35689216]
[18]
Hu H, Chen Y, Jing L, Zhai C, Shen L. The link between ferroptosis and cardiovascular diseases: A novel target for treatment. Front Cardiovasc Med 2021; 8: 710963.
[http://dx.doi.org/10.3389/fcvm.2021.710963] [PMID: 34368260]
[19]
Hou Y, Wei Y, Lautrup S, et al. NAD + supplementation reduces neuroinflammation and cell senescence in a transgenic mouse model of Alzheimer’s disease via cGAS–STING. Proc Natl Acad Sci 2021; 118(37): e2011226118.
[http://dx.doi.org/10.1073/pnas.2011226118] [PMID: 34497121]
[20]
Oduro PK, Zheng X, Wei J, et al. The cGAS–STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy. Acta Pharm Sin B 2022; 12(1): 50-75.
[http://dx.doi.org/10.1016/j.apsb.2021.05.011] [PMID: 35127372]
[21]
Hu S, Gao Y, Gao R, et al. The selective STING inhibitor H-151 preserves myocardial function and ameliorates cardiac fibrosis in murine myocardial infarction. Int Immunopharmacol 2022; 107: 108658.
[http://dx.doi.org/10.1016/j.intimp.2022.108658] [PMID: 35278833]
[22]
Lu GF, Chen SC, Xia YP, Ye ZM, Cao F, Hu B. Synergistic inflammatory signaling by cGAS may be involved in the development of atherosclerosis. Aging 2021; 13(4): 5650-73.
[http://dx.doi.org/10.18632/aging.202491] [PMID: 33589571]
[23]
Taguchi T, Mukai K, Takaya E, Shindo R. STING operation at the ER/golgi interface. Front Immunol 2021; 12: 646304.
[http://dx.doi.org/10.3389/fimmu.2021.646304] [PMID: 34012437]
[24]
Barber GN. STING: infection, inflammation and cancer. Nat Rev Immunol 2015; 15(12): 760-70.
[http://dx.doi.org/10.1038/nri3921] [PMID: 26603901]
[25]
Shu C, Yi G, Watts T, Kao CC, Li P. Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system. Nat Struct Mol Biol 2012; 19(7): 722-4.
[http://dx.doi.org/10.1038/nsmb.2331] [PMID: 22728658]
[26]
Wu J, Yan N. STIM1 moonlights as an anchor for STING. Nat Immunol 2019; 20(2): 112-4.
[http://dx.doi.org/10.1038/s41590-018-0300-2] [PMID: 30643261]
[27]
Abe T, Barber GN. Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-κB activation through TBK1. J Virol 2014; 88(10): 5328-41.
[http://dx.doi.org/10.1128/JVI.00037-14] [PMID: 24600004]
[28]
Lippai D, Bala S, Petrasek J, et al. Alcohol-induced IL-1β in the brain is mediated by NLRP3/ASC inflammasome activation that amplifies neuroinflammation. J Leukoc Biol 2013; 94(1): 171-82.
[http://dx.doi.org/10.1189/jlb.1212659] [PMID: 23625200]
[29]
Wan D, Jiang W, Hao J. Research advances in how the cGAS-STING pathway controls the cellular inflammatory response. Front Immunol 2020; 11: 615.
[http://dx.doi.org/10.3389/fimmu.2020.00615] [PMID: 32411126]
[30]
Sun L, Wu J, Du F, Chen X, Chen ZJ. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 2013; 339(6121): 786-91.
[http://dx.doi.org/10.1126/science.1232458] [PMID: 23258413]
[31]
Li Y, Wilson HL, Kiss-Toth E. Regulating STING in health and disease. J Inflamm 2017; 14(1): 11.
[http://dx.doi.org/10.1186/s12950-017-0159-2] [PMID: 28596706]
[32]
Muskardin TLW, Niewold TB. Type I interferon in rheumatic diseases. Nat Rev Rheumatol 2018; 14(4): 214-28.
[http://dx.doi.org/10.1038/nrrheum.2018.31] [PMID: 29559718]
[33]
Thim-uam A, Prabakaran T, Tansakul M, et al. STING mediates lupus via the activation of conventional dendritic cell maturation and plasmacytoid dendritic cell differentiation. iScience 2020; 23(9): 101530.
[http://dx.doi.org/10.1016/j.isci.2020.101530] [PMID: 33083760]
[34]
Zhang Y, Ma Z, Wang Y, et al. Streptavidin promotes DNA binding and activation of cGAS to enhance innate immunity. iScience 2020; 23(9): 101463.
[http://dx.doi.org/10.1016/j.isci.2020.101463] [PMID: 32861998]
[35]
Motedayen Aval L, Pease JE, Sharma R, Pinato DJ. Challenges and opportunities in the clinical development of STING agonists for cancer immunotherapy. J Clin Med 2020; 9(10): 3323.
[http://dx.doi.org/10.3390/jcm9103323] [PMID: 33081170]
[36]
Zhang X, Bai X, Chen ZJ. Structures and mechanisms in the cGAS-STING innate immunity pathway. Immunity 2020; 53(1): 43-53.
[http://dx.doi.org/10.1016/j.immuni.2020.05.013] [PMID: 32668227]
[37]
Ma XM, Geng K, Law BY, et al. Lipotoxicity-induced mtDNA release promotes diabetic cardiomyopathy by activating the cGAS-STING pathway in obesity-related diabetes. Cell Biol Toxicol 2022; 39(1): 277-99.
[PMID: 35235096]
[38]
Hu D, Cui YX, Wu MY, et al. Cytosolic DNA sensor cGAS plays an essential pathogenetic role in pressure overload-induced heart failure. Am J Physiol Heart Circ Physiol 2020; 318(6): H1525-37.
[http://dx.doi.org/10.1152/ajpheart.00097.2020] [PMID: 32383996]
[39]
Cao DJ, Schiattarella GG, Villalobos E, et al. Cytosolic DNA sensing promotes macrophage transformation and governs myocardial ischemic injury. Circulation 2018; 137(24): 2613-34.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.031046] [PMID: 29437120]
[40]
Mallavia B, Liu F, Lefrançais E, et al. Mitochondrial DNA stimulates TLR9-dependent neutrophil extracellular trap formation in primary graft dysfunction. Am J Respir Cell Mol Biol 2020; 62(3): 364-72.
[http://dx.doi.org/10.1165/rcmb.2019-0140OC] [PMID: 31647878]
[41]
Liu ML, Lyu X, Werth VP. Recent progress in the mechanistic understanding of NET formation in neutrophils. FEBS J 2022; 289(14): 3954-66.
[http://dx.doi.org/10.1111/febs.16036] [PMID: 34042290]
[42]
Liu L, Mao Y, Xu B, et al. Induction of neutrophil extracellular traps during tissue injury: Involvement of STING and Toll‐like receptor 9 pathways. Cell Prolif 2019; 52(3): e12579.
[http://dx.doi.org/10.1111/cpr.12579] [PMID: 30851061]
[43]
Yu H, Liu Q, Guo Y, Xia Y, Luo S. Palmitic acid suppresses autophagy in neonatal rat cardiomyocytes via the cGAS-STING-IRF3 pathway. Nan Fang Yi Ke Da Xue Xue Bao 2022; 42(1): 36-44.
[PMID: 35249868]
[44]
Zhu Y, Deng J, Nan ML, et al. The Interplay Between Pattern Recognition Receptors and Autophagy in Inflammation. Adv Exp Med Biol 2019; 1209: 79-108.
[http://dx.doi.org/10.1007/978-981-15-0606-2_6] [PMID: 31728866]
[45]
Liang Q, Seo GJ, Choi YJ, et al. Crosstalk between the cGAS DNA sensor and Beclin-1 autophagy protein shapes innate antimicrobial immune responses. Cell Host Microbe 2014; 15(2): 228-38.
[http://dx.doi.org/10.1016/j.chom.2014.01.009] [PMID: 24528868]
[46]
Konno H, Konno K, Barber GN. Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling. Cell 2013; 155(3): 688-98.
[http://dx.doi.org/10.1016/j.cell.2013.09.049] [PMID: 24119841]
[47]
Watson RO, Manzanillo PS, Cox JS. Extracellular M. tuberculosis DNA targets bacteria for autophagy by activating the host DNA-sensing pathway. Cell 2012; 150(4): 803-15.
[http://dx.doi.org/10.1016/j.cell.2012.06.040] [PMID: 22901810]
[48]
Nakahira K, Haspel JA, Rathinam VAK, et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol 2011; 12(3): 222-30.
[http://dx.doi.org/10.1038/ni.1980] [PMID: 21151103]
[49]
Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature 2011; 469(7329): 221-5.
[http://dx.doi.org/10.1038/nature09663] [PMID: 21124315]
[50]
Qiu Z, Lei S, Zhao B, et al. NLRP3 inflammasome activation-mediated pyroptosis aggravates myocardial ischemia/reperfusion injury in diabetic rats. Oxid Med Cell Longev 2017; 2017: 1-17.
[http://dx.doi.org/10.1155/2017/9743280] [PMID: 29062465]
[51]
Bai L, Dai J, Xia Y, et al. Hydrogen sulfide ameliorated high choline-induced cardiac dysfunction by inhibiting cGAS-STING-NLRP3 inflammasome pathway. Oxid Med Cell Longev 2022; 2022: 1-12.
[http://dx.doi.org/10.1155/2022/1392896] [PMID: 35910846]
[52]
Li N, Zhou H, Wu H, et al. STING-IRF3 contributes to lipopolysaccharide-induced cardiac dysfunction, inflammation, apoptosis and pyroptosis by activating NLRP3. Redox Biol 2019; 24: 101215.
[http://dx.doi.org/10.1016/j.redox.2019.101215] [PMID: 31121492]
[53]
Zhang W, Li G, Luo R, et al. Cytosolic escape of mitochondrial DNA triggers cGAS-STING-NLRP3 axis-dependent nucleus pulposus cell pyroptosis. Exp Mol Med 2022; 54(2): 129-42.
[http://dx.doi.org/10.1038/s12276-022-00729-9] [PMID: 35145201]
[54]
Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 2015; 526(7575): 660-5.
[http://dx.doi.org/10.1038/nature15514] [PMID: 26375003]
[55]
Sborgi L, Rühl S, Mulvihill E, et al. GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death. EMBO J 2016; 35(16): 1766-78.
[http://dx.doi.org/10.15252/embj.201694696] [PMID: 27418190]
[56]
Yu Y, Yan Y, Niu F, et al. Ferroptosis: a cell death connecting oxidative stress, inflammation and cardiovascular diseases. Cell Death Discov 2021; 7(1): 193.
[http://dx.doi.org/10.1038/s41420-021-00579-w] [PMID: 34312370]
[57]
Yang K, Song H, Yin D. PDSS2 inhibits the ferroptosis of vascular endothelial cells in atherosclerosis by activating Nrf2. J Cardiovasc Pharmacol 2021; 77(6): 767-76.
[http://dx.doi.org/10.1097/FJC.0000000000001030] [PMID: 33929387]
[58]
Kong C, Ni X, Wang Y, et al. ICA69 aggravates ferroptosis causing septic cardiac dysfunction via STING trafficking. Cell Death Discov 2022; 8(1): 187.
[http://dx.doi.org/10.1038/s41420-022-00957-y] [PMID: 35397620]
[59]
Kuang F, Liu J, Li C, Kang R, Tang D. Cathepsin B is a mediator of organelle-specific initiation of ferroptosis. Biochem Biophys Res Commun 2020; 533(4): 1464-9.
[http://dx.doi.org/10.1016/j.bbrc.2020.10.035] [PMID: 33268027]
[60]
Li C, Zhang Y, Liu J, Kang R, Klionsky DJ, Tang D. Mitochondrial DNA stress triggers autophagy-dependent ferroptotic death. Autophagy 2021; 17(4): 948-60.
[http://dx.doi.org/10.1080/15548627.2020.1739447] [PMID: 32186434]
[61]
Dai E, Han L, Liu J, et al. Ferroptotic damage promotes pancreatic tumorigenesis through a TMEM173/STING-dependent DNA sensor pathway. Nat Commun 2020; 11(1): 6339.
[http://dx.doi.org/10.1038/s41467-020-20154-8] [PMID: 33311482]
[62]
Olagnier D, Brandtoft AM, Gunderstofte C, et al. Nrf2 negatively regulates STING indicating a link between antiviral sensing and metabolic reprogramming. Nat Commun 2018; 9(1): 3506.
[http://dx.doi.org/10.1038/s41467-018-05861-7] [PMID: 30158636]
[63]
Mao H, Zhao Y, Li H, Lei L. Ferroptosis as an emerging target in inflammatory diseases. Prog Biophys Mol Biol 2020; 155: 20-8.
[http://dx.doi.org/10.1016/j.pbiomolbio.2020.04.001] [PMID: 32311424]
[64]
Lv N, Zhao Y, Liu X, et al. Dysfunctional telomeres through mitostress‐induced cGAS/STING activation to aggravate immune senescence and viral pneumonia. Aging Cell 2022; 21(4): e13594.
[http://dx.doi.org/10.1111/acel.13594] [PMID: 35313074]
[65]
Liu F, Liu Y, Zhuang Z, et al. Beclin1 Haploinsufficiency accentuates second-hand smoke exposure -induced myocardial Remodeling and contractile dysfunction through a STING-mediated mechanism. J Mol Cell Cardiol 2020; 148: 78-88.
[http://dx.doi.org/10.1016/j.yjmcc.2020.08.016] [PMID: 32891637]
[66]
Nakamura M, Sadoshima J. Cardiomyopathy in obesity, insulin resistance and diabetes. J Physiol 2020; 598(14): 2977-93.
[http://dx.doi.org/10.1113/JP276747] [PMID: 30869158]
[67]
Halade GV, Lee DH. Inflammation and resolution signaling in cardiac repair and heart failure. EBioMedicine 2022; 79: 103992.
[http://dx.doi.org/10.1016/j.ebiom.2022.103992] [PMID: 35405389]
[68]
Duncan SE, Gao S, Sarhene M, et al. Macrophage activities in myocardial infarction and heart failure. Cardiol Res Pract 2020; 2020: 1-16.
[http://dx.doi.org/10.1155/2020/4375127] [PMID: 32377427]
[69]
Huangfu N, Wang Y, Xu Z, et al. TDP43 exacerbates atherosclerosis progression by promoting inflammation and lipid uptake of macrophages. Front Cell Dev Biol 2021; 9: 687169.
[http://dx.doi.org/10.3389/fcell.2021.687169] [PMID: 34291051]
[70]
Mao Y, Luo W, Zhang L, et al. STING–IRF3 triggers endothelial inflammation in response to free fatty acid-induced mitochondrial damage in diet-induced obesity. Arterioscler Thromb Vasc Biol 2017; 37(5): 920-9.
[http://dx.doi.org/10.1161/ATVBAHA.117.309017] [PMID: 28302626]
[71]
Wang C, Zhu L, Yuan W, et al. Diabetes aggravates myocardial ischaemia reperfusion injury via activating Nox2‐related programmed cell death in an AMPK‐dependent manner. J Cell Mol Med 2020; 24(12): 6670-9.
[http://dx.doi.org/10.1111/jcmm.15318] [PMID: 32351005]
[72]
Liao JK. Linking endothelial dysfunction with endothelial cell activation. J Clin Invest 2013; 123(2): 540-1.
[http://dx.doi.org/10.1172/JCI66843] [PMID: 23485580]
[73]
Yuan L, Mao Y, Luo W, et al. Palmitic acid dysregulates the Hippo–YAP pathway and inhibits angiogenesis by inducing mitochondrial damage and activating the cytosolic DNA sensor cGAS–STING–IRF3 signaling mechanism. J Biol Chem 2017; 292(36): 15002-15.
[http://dx.doi.org/10.1074/jbc.M117.804005] [PMID: 28698384]
[74]
Reed GW, Rossi JE, Cannon CP. Acute myocardial infarction. Lancet 2017; 389(10065): 197-210.
[http://dx.doi.org/10.1016/S0140-6736(16)30677-8] [PMID: 27502078]
[75]
King KR, Aguirre AD, Ye YX, et al. IRF3 and type I interferons fuel a fatal response to myocardial infarction. Nat Med 2017; 23(12): 1481-7.
[http://dx.doi.org/10.1038/nm.4428] [PMID: 29106401]
[76]
Rech L, Abdellatif M, Pöttler M, et al. Small molecule STING inhibition improves myocardial infarction remodeling. Life Sci 2022; 291: 120263.
[http://dx.doi.org/10.1016/j.lfs.2021.120263] [PMID: 34971697]
[77]
Hofbauer TM, Mangold A, Scherz T, et al. Neutrophil extracellular traps and fibrocytes in ST-segment elevation myocardial infarction. Basic Res Cardiol 2019; 114(5): 33.
[http://dx.doi.org/10.1007/s00395-019-0740-3] [PMID: 31312919]
[78]
Han W, Du C, Zhu Y, et al. Targeting myocardial mitochondria-STING-polyamine axis prevents cardiac hypertrophy in chronic kidney disease. JACC Basic Transl Sci 2022; 7(8): 820-40.
[http://dx.doi.org/10.1016/j.jacbts.2022.03.006] [PMID: 36061341]
[79]
Choudhuri S, Garg NJ. PARP1-cGAS-NF-κB pathway of proinflammatory macrophage activation by extracellular vesicles released during Trypanosoma cruzi infection and Chagas disease. PLoS Pathog 2020; 16(4): e1008474.
[http://dx.doi.org/10.1371/journal.ppat.1008474] [PMID: 32315358]
[80]
Gong Y, Li G, Tao J, et al. Double knockout of Akt2 and AMPK accentuates high fat diet-induced cardiac anomalies through a cGAS-STING-mediated mechanism. Biochim Biophys Acta Mol Basis Dis 2020; 1866(10): 165855.
[http://dx.doi.org/10.1016/j.bbadis.2020.165855] [PMID: 32512189]
[81]
Ling S, Xu JW. NETosis as a pathogenic factor for heart failure. Oxid Med Cell Longev 2021; 2021: 1-24.
[http://dx.doi.org/10.1155/2021/6687096] [PMID: 33680285]
[82]
Dick SA, Epelman S. Chronic heart failure and inflammation. Circ Res 2016; 119(1): 159-76.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.308030] [PMID: 27340274]
[83]
Hinman A, Holst CR, Latham JC, et al. Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase. PLoS One 2018; 13(8): e0201369.
[http://dx.doi.org/10.1371/journal.pone.0201369] [PMID: 30110365]
[84]
Vincent J, Adura C, Gao P, et al. Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice. Nat Commun 2017; 8(1): 750.
[http://dx.doi.org/10.1038/s41467-017-00833-9] [PMID: 28963528]
[85]
Hall J, Brault A, Vincent F, et al. Discovery of PF-06928215 as a high affinity inhibitor of cGAS enabled by a novel fluorescence polarization assay. PLoS One 2017; 12(9): e0184843.
[http://dx.doi.org/10.1371/journal.pone.0184843] [PMID: 28934246]
[86]
Haag SM, Gulen MF, Reymond L, et al. Targeting STING with covalent small-molecule inhibitors. Nature 2018; 559(7713): 269-73.
[http://dx.doi.org/10.1038/s41586-018-0287-8] [PMID: 29973723]
[87]
Guerini D. STING agonists/antagonists: their potential as therapeutics and future developments. Cells 2022; 11(7): 1159.
[http://dx.doi.org/10.3390/cells11071159] [PMID: 35406723]
[88]
Zhao Q, Manohar M, Wei Y, Pandol SJ, Habtezion A. STING signalling protects against chronic pancreatitis by modulating Th17 response. Gut 2019; 68(10): 1827-37.
[http://dx.doi.org/10.1136/gutjnl-2018-317098] [PMID: 30705050]
[89]
Zhao Q, Wei Y, Pandol SJ, Li L, Habtezion A. STING signaling promotes inflammation in experimental acute pancreatitis. Gastroenterology 2018; 154(6): 1822-1835.e2.
[http://dx.doi.org/10.1053/j.gastro.2018.01.065] [PMID: 29425920]
[90]
Xiong R, Li N, Chen L, et al. STING protects against cardiac dysfunction and remodelling by blocking autophagy. Cell Commun Signal 2021; 19(1): 109.
[http://dx.doi.org/10.1186/s12964-021-00793-0] [PMID: 34749750]