Angiogenesis, Inflammation & Therapeutics | Online ISSN  2207-872X
REVIEWS   (Open Access)

The cGAS–STING Pathway is A Source of Potential Therapeutic Targets for Atherosclerosis Treatment

Anastasia V. Poznyak 1*, Nikolay A. Orekhov 2, Tatiana Ivanovna Kovyanova 1,3, Irina Alexandrovna Starodubtseva 4, Natalia V. Elizova 2, Vasily N. Sukhorukov 3, Alexander N. Orekhov 3

+ Author Affiliations

Journal of Angiotherapy 8(6) 1-13 https://doi.org/10.25163/angiotherapy.869749

Submitted: 23 April 2024  Revised: 19 June 2024  Published: 22 June 2024 

Abstract

The cyclic GMP-AMP synthase (cGAS) – stimulator of interferon genes (STING) pathway presents promising therapeutic targets for the treatment of atherosclerosis. This review article explores the discovery of DNA sensing by cGAS-STING, insights into the signal transduction cascade of the pathway, its activation in disease contexts, and its role in senescence, autoimmune and inflammatory diseases. Furthermore, the article delves into the involvement of STIM1 in atherosclerotic plaque development and investigates the potential regulatory mechanisms of STIM1/cGAS-STING in atherosclerosis. Overall, a comprehensive understanding of the cGAS-STING pathway's role in inflammatory and autoimmune disorders may offer new perspectives for developing treatments for these conditions.

Keywords: cGAS-STING pathway, DNA sensing, Innate immunity, Cyclic GMP-AMP synthase, Antiviral response

References

Afzali, B., Lombardi, G., Lechler, R. I., & Lord, G. M. (2007). The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clinical and experimental immunology, 148(1), 32–46. https://doi.org/10.1111/j.1365-2249.2007.03356.x

An, C., Li, Z., Chen, Y., Huang, S., Yang, F., Hu, Y., Xu, T., Zhang, C., & Ge, S. (2024). The cGAS-STING pathway in cardiovascular diseases: from basic research to clinical perspectives. Cell & bioscience, 14(1), 58. https://doi.org/10.1186/s13578-024-01242-4

Bai, S., Wei, Y., Hou, W., Yao, Y., Zhu, J., Hu, X., Chen, W., Du, Y., He, W., Shen, B., & Du, J. (2020). Orai-IGFBP3 signaling complex regulates high-glucose exposure-induced increased proliferation, permeability, and migration of human coronary artery endothelial cells. BMJ open diabetes research & care, 8(1), e001400. https://doi.org/10.1136/bmjdrc-2020-001400

Bao, T., Liu, J., Leng, J., & Cai, L. (2021). The cGAS-STING pathway: more than fighting against viruses and cancer. Cell & bioscience, 11(1), 209. https://doi.org/10.1186/s13578-021-00724-z

Bekkering, S., Quintin, J., Joosten, L. A., van der Meer, J. W., Netea, M. G., & Riksen, N. P. (2014). Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell formation via epigenetic reprogramming of monocytes. Arteriosclerosis, thrombosis, and vascular biology, 34(8), 1731–1738. https://doi.org/10.1161/ATVBAHA.114.303887

Bobryshev, Y. V., Ivanova, E. A., Chistiakov, D. A., Nikiforov, N. G., & Orekhov, A. N. (2016). Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis. BioMed research international, 2016, 9582430. https://doi.org/10.1155/2016/9582430

Bryant, F. R., & Benkovic, S. J. (1982). Phosphorothioate substrates for T4 RNA ligase. Biochemistry, 21(23), 5877–5885. https://doi.org/10.1021/bi00266a023

Bu, L. L., Yuan, H. H., Xie, L. L., Guo, M. H., Liao, D. F., & Zheng, X. L. (2023). New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death. International journal of molecular sciences, 24(20), 15160. https://doi.org/10.3390/ijms242015160

Chathuranga, K., Weerawardhana, A., Dodantenna, N., & Lee, J. S. (2021). Regulation of antiviral innate immune signaling and viral evasion following viral genome sensing. Experimental & molecular medicine, 53(11), 1647–1668. https://doi.org/10.1038/s12276-021-00691-y

Chen, C., & Khismatullin, D. B. (2015). Oxidized low-density lipoprotein contributes to atherogenesis via co-activation of macrophages and mast cells. PloS one, 10(3), e0123088. https://doi.org/10.1371/journal.pone.0123088

Coccia, E. M., & Battistini, A. (2015). Early IFN type I response: Learning from microbial evasion strategies. Seminars in immunology, 27(2), 85–101. https://doi.org/10.1016/j.smim.2015.03.005

Danziger, O., Patel, R. S., DeGrace, E. J., Rosen, M. R., & Rosenberg, B. R. (2022). Inducible CRISPR activation screen for interferon-stimulated genes identifies OAS1 as a SARS-CoV-2 restriction factor. PLoS pathogens, 18(4), e1010464. https://doi.org/10.1371/journal.ppat.1010464

David, C., & Frémond, M. L. (2022). Lung Inflammation in STING-Associated Vasculopathy with Onset in Infancy (SAVI). Cells, 11(3), 318. https://doi.org/10.3390/cells11030318

Decout, A., Katz, J. D., Venkatraman, S., & Ablasser, A. (2021). The cGAS-STING pathway as a therapeutic target in inflammatory diseases. Nature reviews. Immunology, 21(9), 548–569. https://doi.org/10.1038/s41577-021-00524-z

Deng, Z., Chong, Z., Law, C. S., Mukai, K., Ho, F. O., Martinu, T., Backes, B. J., Eckalbar, W. L., Taguchi, T., & Shum, A. K. (2020). A defect in COPI-mediated transport of STING causes immune dysregulation in COPA syndrome. The Journal of experimental medicine, 217(11), e20201045. https://doi.org/10.1084/jem.20201045

Ding, C., Song, Z., Shen, A., Chen, T., & Zhang, A. (2020). Small molecules targeting the innate immune cGAS?STING?TBK1 signaling pathway. Acta pharmaceutica Sinica. B, 10(12), 2272–2298. https://doi.org/10.1016/j.apsb.2020.03.001

Dubensky, T. W., Jr, Kanne, D. B., & Leong, M. L. (2013). Rationale, progress and development of vaccines utilizing STING-activating cyclic dinucleotide adjuvants. Therapeutic advances in vaccines, 1(4), 131–143. https://doi.org/10.1177/2051013613501988

Esposito, M., Ruffini, F., Bergami, A., Garzetti, L., Borsellino, G., Battistini, L., Martino, G., & Furlan, R. (2010). IL-17- and IFN-γ-secreting Foxp3+ T cells infiltrate the target tissue in experimental autoimmunity. Journal of immunology (Baltimore, Md. : 1950), 185(12), 7467–7473. https://doi.org/10.4049/jimmunol.1001519

Fang, Q., Tian, M., Wang, F., Zhang, Z., Du, T., Wang, W., Yang, Y., Li, X., Chen, G., Xiao, L., Wei, H., Wang, Y., Chen, C., & Wang, D. W. (2019). Amlodipine induces vasodilation via Akt2/Sp1-activated miR-21 in smooth muscle cells. British journal of pharmacology, 176(13), 2306–2320. https://doi.org/10.1111/bph.14679

Frankowska, N., Lisowska, K., & Witkowski, J. M. (2022). Proteolysis dysfunction in the process of aging and age-related diseases. Frontiers in aging, 3, 927630. https://doi.org/10.3389/fragi.2022.927630

Gan, Y., Li, X., Han, S., Liang, Q., Ma, X., Rong, P., Wang, W., & Li, W. (2022). The cGAS/STING Pathway: A Novel Target for Cancer Therapy. Frontiers in immunology, 12, 795401. https://doi.org/10.3389/fimmu.2021.795401

Gomelsky M. (2011). cAMP, c-di-GMP, c-di-AMP and now cGMP: bacteria use them all!. Molecular microbiology, 79(3), 562–565. https://doi.org/10.1111/j.1365-2958.2010.07514.x

Guimarães, E. S., Marinho, F. V., de Queiroz, N. M. G. P., Antunes, M. M., & Oliveira, S. C. (2021). Impact of STING Inflammatory Signaling during Intracellular Bacterial Infections. Cells, 11(1), 74. https://doi.org/10.3390/cells11010074

Gulen, M. F., Samson, N., Keller, A., Schwabenland, M., Liu, C., Glück, S., Thacker, V. V., Favre, L., Mangeat, B., Kroese, L. J., Krimpenfort, P., Prinz, M., & Ablasser, A. (2023). cGAS-STING drives ageing-related inflammation and neurodegeneration. Nature, 620(7973), 374–380. https://doi.org/10.1038/s41586-023-06373-1

Hall, J., Ralph, E. C., Shanker, S., Wang, H., Byrnes, L. J., Horst, R., Wong, J., Brault, A., Dumlao, D., Smith, J. F., Dakin, L. A., Schmitt, D. C., Trujillo, J., Vincent, F., Griffor, M., & Aulabaugh, A. E. (2017). The catalytic mechanism of cyclic GMP-AMP synthase (cGAS) and implications for innate immunity and inhibition. Protein science : a publication of the Protein Society, 26(12), 2367–2380. https://doi.org/10.1002/pro.3304

Hall, J., Ralph, E. C., Shanker, S., Wang, H., Byrnes, L. J., Horst, R., Wong, J., Brault, A., Dumlao, D., Smith, J. F., Dakin, L. A., Schmitt, D. C., Trujillo, J., Vincent, F., Griffor, M., & Aulabaugh, A. E. (2017). The catalytic mechanism of cyclic GMP-AMP synthase (cGAS) and implications for innate immunity and inhibition. Protein science : a publication of the Protein Society, 26(12), 2367–2380. https://doi.org/10.1002/pro.3304

He, W., Mu, X., Wu, X., Liu, Y., Deng, J., Liu, Y., Han, F., & Nie, X. (2024). The cGAS-STING pathway: a therapeutic target in diabetes and its complications. Burns & trauma, 12, tkad050. https://doi.org/10.1093/burnst/tkad050

Hooy, R. M., & Sohn, J. (2018). The allosteric activation of cGAS underpins its dynamic signaling landscape. eLife, 7, e39984. https://doi.org/10.7554/eLife.39984

Hu, H., Zhao, R., He, Q., Cui, C., Song, J., Guo, X., Zang, N., Yang, M., Zou, Y., Yang, J., Li, J., Wang, L., Xia, L., Wang, L., He, F., Hou, X., Yan, F., & Chen, L. (2022). cGAS-STING mediates cytoplasmic mitochondrial-DNA-induced inflammatory signal transduction during accelerated senescence of pancreatic β-cells induced by metabolic stress. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 36(5), e22266. https://doi.org/10.1096/fj.202101988R

Hu, T., Pan, M., Yin, Y., Wang, C., Cui, Y., & Wang, Q. (2021). The Regulatory Network of Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Pathway in Viral Evasion. Frontiers in microbiology, 12, 790714. https://doi.org/10.3389/fmicb.2021.790714

Kang, Z. P., Wang, M. X., Wu, T. T., Liu, D. Y., Wang, H. Y., Long, J., Zhao, H. M., & Zhong, Y. B. (2021). Curcumin Alleviated Dextran Sulfate Sodium-Induced Colitis by Regulating M1/M2 Macrophage Polarization and TLRs Signaling Pathway. Evidence-based complementary and alternative medicine : eCAM, 2021, 3334994. https://doi.org/10.1155/2021/3334994

Kato, T., Yamamoto, M., Honda, Y., Orimo, T., Sasaki, I., Murakami, K., Hemmi, H., Fukuda-Ohta, Y., Isono, K., Takayama, S., Nakamura, H., Otsuki, Y., Miyamoto, T., Takita, J., Yasumi, T., Nishikomori, R., Matsubayashi, T., Izawa, K., & Kaisho, T. (2021). Augmentation of Stimulator of Interferon Genes-Induced Type I Interferon Production in COPA Syndrome. Arthritis & rheumatology (Hoboken, N.J.), 73(11), 2105–2115. https://doi.org/10.1002/art.41790

Khalil, R., Diab-Assaf, M., & Lemaitre, J. M. (2023). Emerging Therapeutic Approaches to Target the Dark Side of Senescent Cells: New Hopes to Treat Aging as a Disease and to Delay Age-Related Pathologies. Cells, 12(6), 915. https://doi.org/10.3390/cells12060915

Kuchitsu, Y., Mukai, K., Uematsu, R., Takaada, Y., Shinojima, A., Shindo, R., Shoji, T., Hamano, S., Ogawa, E., Sato, R., Miyake, K., Kato, A., Kawaguchi, Y., Nishitani-Isa, M., Izawa, K., Nishikomori, R., Yasumi, T., Suzuki, T., Dohmae, N., Uemura, T., … Taguchi, T. (2023). STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes. Nature cell biology, 25(3), 453–466. https://doi.org/10.1038/s41556-023-01098-9

Lang, R., Li, H., Luo, X., Liu, C., Zhang, Y., Guo, S., Xu, J., Bao, C., Dong, W., & Yu, Y. (2022). Expression and mechanisms of interferon-stimulated genes in viral infection of the central nervous system (CNS) and neurological diseases. Frontiers in immunology, 13, 1008072. https://doi.org/10.3389/fimmu.2022.1008072

Li, Q., Wu, P., Du, Q., Hanif, U., Hu, H., & Li, K. (2024). cGAS-STING, an important signaling pathway in diseases and their therapy. MedComm, 5(4), e511. https://doi.org/10.1002/mco2.511

Li, S., Qian, N., Jiang, C., Zu, W., Liang, A., Li, M., Elledge, S. J., & Tan, X. (2022). Gain-of-function genetic screening identifies the antiviral function of TMEM120A via STING activation. Nature communications, 13(1), 105. https://doi.org/10.1038/s41467-021-27670-1

Li, T., Li, X., Feng, Y., Dong, G., Wang, Y., & Yang, J. (2020). The Role of Matrix Metalloproteinase-9 in Atherosclerotic Plaque Instability. Mediators of inflammation, 2020, 3872367. https://doi.org/10.1155/2020/3872367

Li, X., Shu, C., Yi, G., Chaton, C. T., Shelton, C. L., Diao, J., Zuo, X., Kao, C. C., Herr, A. B., & Li, P. (2013). Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization. Immunity, 39(6), 1019–1031. https://doi.org/10.1016/j.immuni.2013.10.019

Li, X., Zhu, Y., Zhang, X., An, X., Weng, M., Shi, J., Wang, S., Liu, C., Luo, S., & Zheng, T. (2022). An alternatively spliced STING isoform localizes in the cytoplasmic membrane and directly senses extracellular cGAMP. The Journal of clinical investigation, 132(3), e144339. https://doi.org/10.1172/JCI144339

Liu, Y., & Pu, F. (2023). Updated roles of cGAS-STING signaling in autoimmune diseases. Frontiers in immunology, 14, 1254915. https://doi.org/10.3389/fimmu.2023.1254915

Lodola, F., Laforenza, U., Bonetti, E., Lim, D., Dragoni, S., Bottino, C., Ong, H. L., Guerra, G., Ganini, C., Massa, M., Manzoni, M., Ambudkar, I. S., Genazzani, A. A., Rosti, V., Pedrazzoli, P., Tanzi, F., Moccia, F., & Porta, C. (2012). Store-operated Ca2+ entry is remodelled and controls in vitro angiogenesis in endothelial progenitor cells isolated from tumoral patients. PloS one, 7(9), e42541. https://doi.org/10.1371/journal.pone.0042541

Lukhele, S., Boukhaled, G. M., & Brooks, D. G. (2019). Type I interferon signaling, regulation and gene stimulation in chronic virus infection. Seminars in immunology, 43, 101277. https://doi.org/10.1016/j.smim.2019.05.001

Luo, K., Li, N., Ye, W., Gao, H., Luo, X., & Cheng, B. (2022). Activation of Stimulation of Interferon Genes (STING) Signal and Cancer Immunotherapy. Molecules (Basel, Switzerland), 27(14), 4638. https://doi.org/10.3390/molecules27144638

Luo, X., Li, H., Ma, L., Zhou, J., Guo, X., Woo, S. L., Pei, Y., Knight, L. R., Deveau, M., Chen, Y., Qian, X., Xiao, X., Li, Q., Chen, X., Huo, Y., McDaniel, K., Francis, H., Glaser, S., Meng, F., Alpini, G., … Wu, C. (2018). Expression of STING Is Increased in Liver Tissues From Patients With NAFLD and Promotes Macrophage-Mediated Hepatic Inflammation and Fibrosis in Mice. Gastroenterology, 155(6), 1971–1984.e4. https://doi.org/10.1053/j.gastro.2018.09.010

Ma, G., Bi, S., & Zhang, P. (2021). Long non-coding RNA MIAT regulates ox-LDL-induced cell proliferation, migration and invasion by miR-641/STIM1 axis in human vascular smooth muscle cells. BMC cardiovascular disorders, 21(1), 248. https://doi.org/10.1186/s12872-021-02048-9

Ma, X., Xin, D., She, R., Liu, D., Ge, J., & Mei, Z. (2023). Novel insight into cGAS-STING pathway in ischemic stroke: from pre- to post-disease. Frontiers in immunology, 14, 1275408. https://doi.org/10.3389/fimmu.2023.1275408

Martin, G. R., Blomquist, C. M., Henare, K. L., & Jirik, F. R. (2019). Stimulator of interferon genes (STING) activation exacerbates experimental colitis in mice. Scientific reports, 9(1), 14281. https://doi.org/10.1038/s41598-019-50656-5

Matsumiya, T., & Stafforini, D. M. (2010). Function and regulation of retinoic acid-inducible gene-I. Critical reviews in immunology, 30(6), 489–513. https://doi.org/10.1615/critrevimmunol.v30.i6.10

Mbongue, J. C., Nicholas, D. A., Torrez, T. W., Kim, N. S., Firek, A. F., & Langridge, W. H. (2015). The Role of Indoleamine 2, 3-Dioxygenase in Immune Suppression and Autoimmunity. Vaccines, 3(3), 703–729. https://doi.org/10.3390/vaccines3030703

McHugh, D., & Gil, J. (2018). Senescence and aging: Causes, consequences, and therapeutic avenues. The Journal of cell biology, 217(1), 65–77. https://doi.org/10.1083/jcb.201708092

Mohseni, G., Li, J., Ariston Gabriel, A. N., Du, L., Wang, Y. S., & Wang, C. (2021). The Function of cGAS-STING Pathway in Treatment of Pancreatic Cancer. Frontiers in immunology, 12, 781032. https://doi.org/10.3389/fimmu.2021.781032

Motani, K., & Kosako, H. (2018). Activation of stimulator of interferon genes (STING) induces ADAM17-mediated shedding of the immune semaphorin SEMA4D. The Journal of biological chemistry, 293(20), 7717–7726. https://doi.org/10.1074/jbc.RA118.002175

Newman, A. A. C., Serbulea, V., Baylis, R. A., Shankman, L. S., Bradley, X., Alencar, G. F., Owsiany, K., Deaton, R. A., Karnewar, S., Shamsuzzaman, S., Salamon, A., Reddy, M. S., Guo, L., Finn, A., Virmani, R., Cherepanova, O. A., & Owens, G. K. (2021). Multiple cell types contribute to the atherosclerotic lesion fibrous cap by PDGFRβ and bioenergetic mechanisms. Nature metabolism, 3(2), 166–181. https://doi.org/10.1038/s42255-020-00338-8

Oduro, P. K., Zheng, X., Wei, J., Yang, Y., Wang, Y., Zhang, H., Liu, E., Gao, X., Du, M., & Wang, Q. (2022). The cGAS-STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy. Acta pharmaceutica Sinica. B, 12(1), 50–75. https://doi.org/10.1016/j.apsb.2021.05.011

Ou, L., Zhang, A., Cheng, Y., & Chen, Y. (2021). The cGAS-STING Pathway: A Promising Immunotherapy Target. Frontiers in immunology, 12, 795048. https://doi.org/10.3389/fimmu.2021.795048

Pan, J., Fei, C. J., Hu, Y., Wu, X. Y., Nie, L., & Chen, J. (2023). Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases. Zoological research, 44(1), 183–218. https://doi.org/10.24272/j.issn.2095-8137.2022.464

Papinska, J., Bagavant, H., Gmyrek, G. B., Sroka, M., Tummala, S., Fitzgerald, K. A., & Deshmukh, U. S. (2018). Activation of Stimulator of Interferon Genes (STING) and Sjögren Syndrome. Journal of dental research, 97(8), 893–900. https://doi.org/10.1177/0022034518760855

Paul, S. K., Oshima, M., Patil, A., Sone, M., Kato, H., Maezawa, Y., Kaneko, H., Fukuyo, M., Rahmutulla, B., Ouchi, Y., Tsujimura, K., Nakanishi, M., Kaneda, A., Iwama, A., Yokote, K., Eto, K., & Takayama, N. (2024). Retrotransposons in Werner syndrome-derived macrophages trigger type I interferon-dependent inflammation in an atherosclerosis model. Nature communications, 15(1), 4772. https://doi.org/10.1038/s41467-024-48663-w

Piaszyk-Borychowska, A., Széles, L., Csermely, A., Chiang, H. C., Wesoly, J., Lee, C. K., Nagy, L., & Bluyssen, H. A. R. (2019). Signal Integration of IFN-I and IFN-II With TLR4 Involves Sequential Recruitment of STAT1-Complexes and NFκB to Enhance Pro-inflammatory Transcription. Frontiers in immunology, 10, 1253. https://doi.org/10.3389/fimmu.2019.01253

Prantner, D., Perkins, D. J., & Vogel, S. N. (2017). AMP-activated Kinase (AMPK) Promotes Innate Immunity and Antiviral Defense through Modulation of Stimulator of Interferon Genes (STING) Signaling. The Journal of biological chemistry, 292(1), 292–304. https://doi.org/10.1074/jbc.M116.763268

Pu, Z., Lu, J., & Yang, X. (2022). Emerging Roles of Circular RNAs in Vascular Smooth Muscle Cell Dysfunction. Frontiers in genetics, 12, 749296. https://doi.org/10.3389/fgene.2021.749296

Saito, Y., Yamamoto, S., & Chikenji, T. S. (2024). Role of cellular senescence in inflammation and regeneration. Inflammation and regeneration, 44(1), 28. https://doi.org/10.1186/s41232-024-00342-5

Saleh, A., Macia, A., & Muotri, A. R. (2019). Transposable Elements, Inflammation, and Neurological Disease. Frontiers in neurology, 10, 894. https://doi.org/10.3389/fneur.2019.00894

Schmitz, C. R. R., Maurmann, R. M., Guma, F. T. C. R., Bauer, M. E., & Barbé-Tuana, F. M. (2023). cGAS-STING pathway as a potential trigger of immunosenescence and inflammaging. Frontiers in immunology, 14, 1132653. https://doi.org/10.3389/fimmu.2023.1132653

Seok, J. K., Kim, M., Kang, H. C., Cho, Y. Y., Lee, H. S., & Lee, J. Y. (2023). Beyond DNA sensing: expanding the role of cGAS/STING in immunity and diseases. Archives of pharmacal research, 46(6), 500–534. https://doi.org/10.1007/s12272-023-01452-3

Siedel, H., Roers, A., Rösen-Wolff, A., & Luksch, H. (2020). Type I interferon-independent T cell impairment in a Tmem173 N153S/WT mouse model of STING associated vasculopathy with onset in infancy (SAVI). Clinical immunology (Orlando, Fla.), 216, 108466. https://doi.org/10.1016/j.clim.2020.108466

Slavik, K. M., Morehouse, B. R., Ragucci, A. E., Zhou, W., Ai, X., Chen, Y., Li, L., Wei, Z., Bähre, H., König, M., Seifert, R., Lee, A. S. Y., Cai, H., Imler, J. L., & Kranzusch, P. J. (2021). cGAS-like receptors sense RNA and control 3'2'-cGAMP signalling in Drosophila. Nature, 597(7874), 109–113. https://doi.org/10.1038/s41586-021-03743-5

Smith J. A. (2021). STING, the Endoplasmic Reticulum, and Mitochondria: Is Three a Crowd or a Conversation?. Frontiers in immunology, 11, 611347. https://doi.org/10.3389/fimmu.2020.611347

Tan, H. Y., Yong, Y. K., Xue, Y. C., Liu, H., Furihata, T., Shankar, E. M., & Ng, C. S. (2022). cGAS and DDX41-STING mediated intrinsic immunity spreads intercellularly to promote neuroinflammation in SOD1 ALS model. iScience, 25(6), 104404. https://doi.org/10.1016/j.isci.2022.104404

Unterholzner L. (2019). Beyond sensing DNA: a role for cGAS in the detection of extracellular cyclic di-nucleotides. EMBO reports, 20(4), e47970. https://doi.org/10.15252/embr.201947970

Van Giesen, K. J. D., Thompson, M. J., Meng, Q., & Lovelock, S. L. (2022). Biocatalytic Synthesis of Antiviral Nucleosides, Cyclic Dinucleotides, and Oligonucleotide Therapies. JACS Au, 3(1), 13–24. https://doi.org/10.1021/jacsau.2c00481

Verrier, E. R., & Langevin, C. (2021). Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase (cGAS), a Multifaceted Platform of Intracellular DNA Sensing. Frontiers in immunology, 12, 637399. https://doi.org/10.3389/fimmu.2021.637399

Verrier, E. R., & Langevin, C. (2021). Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase (cGAS), a Multifaceted Platform of Intracellular DNA Sensing. Frontiers in immunology, 12, 637399. https://doi.org/10.3389/fimmu.2021.637399

Wan, D., Jiang, W., & Hao, J. (2020). Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response. Frontiers in immunology, 11, 615. https://doi.org/10.3389/fimmu.2020.00615

Wang, B., Zhang, L., Dai, T., Qin, Z., Lu, H., Zhang, L., & Zhou, F. (2021). Liquid-liquid phase separation in human health and diseases. Signal transduction and targeted therapy, 6(1), 290. https://doi.org/10.1038/s41392-021-00678-1

Wang, L. Y., Zhang, J. H., Yu, J., Yang, J., Deng, M. Y., Kang, H. L., & Huang, L. (2015). Reduction of Store-Operated Ca(2+) Entry Correlates with Endothelial Progenitor Cell Dysfunction in Atherosclerotic Mice. Stem cells and development, 24(13), 1582–1590. https://doi.org/10.1089/scd.2014.0538

Wang, X., Wang, Y., Cao, A., Luo, Q., Chen, D., Zhao, W., Xu, J., Li, Q., Bu, X., & Quan, J. (2023). Development of cyclopeptide inhibitors of cGAS targeting protein-DNA interaction and phase separation. Nature communications, 14(1), 6132. https://doi.org/10.1038/s41467-023-41892-5

Wang, Y., Wang, F., & Zhang, X. (2021). STING-associated vasculopathy with onset in infancy: a familial case series report and literature review. Annals of translational medicine, 9(2), 176. https://doi.org/10.21037/atm-20-6198

Warner, J. D., Irizarry-Caro, R. A., Bennion, B. G., Ai, T. L., Smith, A. M., Miner, C. A., Sakai, T., Gonugunta, V. K., Wu, J., Platt, D. J., Yan, N., & Miner, J. J. (2017). STING-associated vasculopathy develops independently of IRF3 in mice. The Journal of experimental medicine, 214(11), 3279–3292. https://doi.org/10.1084/jem.20171351

Whiteley, A. T., Eaglesham, J. B., de Oliveira Mann, C. C., Morehouse, B. R., Lowey, B., Nieminen, E. A., Danilchanka, O., King, D. S., Lee, A. S. Y., Mekalanos, J. J., & Kranzusch, P. J. (2019). Bacterial cGAS-like enzymes synthesize diverse nucleotide signals. Nature, 567(7747), 194–199. https://doi.org/10.1038/s41586-019-0953-5

Yang, Y., Wang, L., Peugnet-González, I., Parada-Venegas, D., Dijkstra, G., & Faber, K. N. (2023). cGAS-STING signaling pathway in intestinal homeostasis and diseases. Frontiers in immunology, 14, 1239142. https://doi.org/10.3389/fimmu.2023.1239142

Yu, L., & Liu, P. (2021). Cytosolic DNA sensing by cGAS: regulation, function, and human diseases. Signal transduction and targeted therapy, 6(1), 170. https://doi.org/10.1038/s41392-021-00554-y

Yu, Y., Liu, J., Liu, C., Liu, R., Liu, L., Yu, Z., Zhuang, J., & Sun, C. (2022). Post-Translational Modifications of cGAS-STING: A Critical Switch for Immune Regulation. Cells, 11(19), 3043. https://doi.org/10.3390/cells11193043

Zevini, A., Olagnier, D., & Hiscott, J. (2017). Crosstalk between Cytoplasmic RIG-I and STING Sensing Pathways. Trends in immunology, 38(3), 194–205. https://doi.org/10.1016/j.it.2016.12.004

Zhai, H., Liu, H., Shang, B., & Zou, X. (2023). Sarsasapogenin blocks ox-LDL-stimulated vascular smooth muscle cell proliferation, migration, and invasion through suppressing STIM1 expression. Cardiovascular diagnosis and therapy, 13(3), 441–452. https://doi.org/10.21037/cdt-23-111

Zhang, Q., Shen, L., Ruan, H., & Huang, Z. (2024). cGAS-STING signaling in cardiovascular diseases. Frontiers in immunology, 15, 1402817. https://doi.org/10.3389/fimmu.2024.1402817

Zhang, X., Shi, H., Wu, J., Zhang, X., Sun, L., Chen, C., & Chen, Z. J. (2013). Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Molecular cell, 51(2), 226–235. https://doi.org/10.1016/j.molcel.2013.05.022

Zhang, Z., Zhou, H., Ouyang, X., Dong, Y., Sarapultsev, A., Luo, S., & Hu, D. (2022). Multifaceted functions of STING in human health and disease: from molecular mechanism to targeted strategy. Signal transduction and targeted therapy, 7(1), 394. https://doi.org/10.1038/s41392-022-01252-z

Zhao, Q., Manohar, M., Wei, Y., Pandol, S. J., & Habtezion, A. (2019). STING signalling protects against chronic pancreatitis by modulating Th17 response. Gut, 68(10), 1827–1837. https://doi.org/10.1136/gutjnl-2018-317098

Zheng, J., Mo, J., Zhu, T., Zhuo, W., Yi, Y., Hu, S., Yin, J., Zhang, W., Zhou, H., & Liu, Z. (2020). Comprehensive elaboration of the cGAS-STING signaling axis in cancer development and immunotherapy. Molecular cancer, 19(1), 133. https://doi.org/10.1186/s12943-020-01250-1

Zheng, W., Liu, A., Xia, N., Chen, N., Meurens, F., & Zhu, J. (2023). How the Innate Immune DNA Sensing cGAS-STING Pathway Is Involved in Apoptosis. International journal of molecular sciences, 24(3), 3029. https://doi.org/10.3390/ijms24033029

Zhou, J., Zhuang, Z., Li, J., & Feng, Z. (2023). Significance of the cGAS-STING Pathway in Health and Disease. International journal of molecular sciences, 24(17), 13316. https://doi.org/10.3390/ijms241713316

Zhuang, H., Lv, Q., Zhong, C., Cui, Y., He, L., Zhang, C., & Yu, J. (2021). Tiliroside Ameliorates Ulcerative Colitis by Restoring the M1/M2 Macrophage Balance via the HIF-1α/glycolysis Pathway. Frontiers in immunology, 12, 649463. https://doi.org/10.3389/fimmu.2021.649463

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