{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:18:07Z","timestamp":1787894287382,"version":"build-2784847793"},"reference-count":127,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82607575"],"award-info":[{"award-number":["82607575"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82607575"],"award-info":[{"award-number":["82607575"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016806","name":"Nantong Natural Science Foundation","doi-asserted-by":"crossref","award":["JC2023042"],"award-info":[{"award-number":["JC2023042"]}],"id":[{"id":"10.13039\/100016806","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The interferon regulatory factor (IRF) family exerts dual regulatory roles in vascular inflammation. Pro-inflammatory IRF1\/3\/5\/7 drive endothelial dysfunction, macrophage M1 polarization, vascular smooth muscle cell (VSMC) transdifferentiation, and adaptive immune amplification via nuclear factor-\u03baB (NF-\u03baB), NOD-like receptor pyrin domain-containing 3 (NLRP3), cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING), and Janus kinase\/signal transducer and activator of transcription (JAK\/STAT) pathways. Conversely, IRF4\/8 mediate anti-inflammatory effects by promoting M2 polarization, reverse cholesterol transport, and dendritic cell regulation. In atherosclerosis, IRFs display spatiotemporal specificity: endothelial IRF3 in early stages, macrophage IRF1\/5 in mid-stages, and smooth muscle IRF7\/IRF8 in late stages, supporting phase-specific precision interventions\u2014early IRF3 blockade, mid-stage modulation of IRF5\/IRF4 balance, and late combined inhibition of IRF7\/8 to stabilize plaques. IRFs also critically participate in hypertensive remodeling, acute coronary syndrome, heart failure, and aortic aneurysm through conserved innate and adaptive immune axes, highlighting their potential as cross-disease biomarkers and therapeutic targets. Major challenges include network redundancy and functional compensation, necessitating single-cell multi-omics and targeted delivery systems for spatiotemporally precise, individualized modulation.<\/jats:p>","DOI":"10.3390\/ijms27177647","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:59:23Z","timestamp":1787741963000},"page":"7647","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interferon Regulatory Factors as Potential Therapeutic Targets in Cardiovascular Disease: Focusing on Vascular Inflammation"],"prefix":"10.3390","volume":"27","author":[{"given":"Chenxi","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Medicine, Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global Burden of Cardiovascular Diseases and Risk Factors, 1990\u20132019: Update from the GBD 2019 Study","volume":"76","author":"Roth","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","unstructured":"World Health Organization (2018). Noncommunicable Diseases Country Profiles 2018, World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41572-019-0106-z","article-title":"Atherosclerosis","volume":"5","author":"Libby","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1161\/CIRCRESAHA.115.307611","article-title":"Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease","volume":"118","author":"Herrington","year":"2016","journal-title":"Circ. Res."},{"key":"ref_5","first-page":"e38","article-title":"Heart Disease and Stroke Statistics-2016 Update: A Report from the American Heart Association","volume":"133","author":"Mozaffarian","year":"2016","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41586-021-03392-8","article-title":"The changing landscape of atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1161\/CIRCRESAHA.118.313591","article-title":"Immunity and Inflammation in Atherosclerosis","volume":"124","author":"Wolf","year":"2019","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1161\/ATVBAHA.108.179564","article-title":"The LDL receptor","volume":"29","author":"Goldstein","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S419","DOI":"10.1016\/S0002-8703(99)70266-8","article-title":"Atherosclerosis is an inflammatory disease","volume":"138","author":"Ross","year":"1999","journal-title":"Am. Heart J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/ni.2001","article-title":"The immune system in atherosclerosis","volume":"12","author":"Hansson","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1161\/ATVBAHA.108.179697","article-title":"Oxidized low-density lipoprotein and atherosclerosis","volume":"30","author":"Steinberg","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1083\/jcb.201412052","article-title":"Recent insights into the cellular biology of atherosclerosis","volume":"209","author":"Tabas","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/apha.12725","article-title":"Effects of shear stress on endothelial cells: Go with the flow","volume":"219","author":"Chistiakov","year":"2017","journal-title":"Acta Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1161\/CIRCRESAHA.117.309715","article-title":"Gut Microbiota in Cardiovascular Health and Disease","volume":"120","author":"Tang","year":"2017","journal-title":"Circ. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1161\/ATVBAHA.108.179705","article-title":"Inflammation in atherosclerosis","volume":"32","author":"Libby","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/j.jacc.2009.09.009","article-title":"Inflammation in atherosclerosis: From pathophysiology to practice","volume":"54","author":"Libby","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/S0008-6363(98)00276-4","article-title":"Atherosclerotic plaque rupture--pathologic basis of plaque stability and instability","volume":"41","author":"Becker","year":"1999","journal-title":"Cardiovasc. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/joim.12862","article-title":"Anti-inflammatory therapy for atherosclerosis: Interpreting divergent results from the CANTOS and CIRT clinical trials","volume":"285","author":"Ridker","year":"2019","journal-title":"J. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nri3520","article-title":"Macrophages in atherosclerosis: A dynamic balance","volume":"13","author":"Moore","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1016\/j.jacc.2018.08.1043","article-title":"Inflammation, Immunity, and Infection in Atherothrombosis: JACC Review Topic of the Week","volume":"72","author":"Libby","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1146\/annurev.immunol.26.021607.090400","article-title":"The IRF family transcription factors in immunity and oncogenesis","volume":"26","author":"Tamura","year":"2008","journal-title":"Annu. Rev. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s00262-009-0804-6","article-title":"Regulation of immunity and oncogenesis by the IRF transcription factor family","volume":"59","author":"Savitsky","year":"2010","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nri1900","article-title":"IRFs: Master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors","volume":"6","author":"Honda","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1146\/annurev.immunol.19.1.623","article-title":"IRF family of transcription factors as regulators of host defense","volume":"19","author":"Taniguchi","year":"2001","journal-title":"Annu. Rev. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wang, Y., Fang, T., Zheng, X., and Huangfu, N. (2025). The role of interferon regulatory factors in atherosclerosis. Front. Cardiovasc. Med., 12.","DOI":"10.3389\/fcvm.2025.1606034"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1161\/CIRCULATIONAHA.116.026046","article-title":"Interferon Regulatory Factor 4 Inhibits Neointima Formation by Engaging Kruppel-Like Factor 4 Signaling","volume":"136","author":"Cheng","year":"2017","journal-title":"Circulation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1161\/CIRCULATIONAHA.117.027844","article-title":"Interferon Regulatory Factor 5 Controls Necrotic Core Formation in Atherosclerotic Lesions by Impairing Efferocytosis","volume":"136","author":"Seneviratne","year":"2017","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4688","DOI":"10.7150\/thno.36862","article-title":"Absence of Interferon Regulatory Factor 1 Protects Against Atherosclerosis in Apolipoprotein E-Deficient Mice","volume":"9","author":"Du","year":"2019","journal-title":"Theranostics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.2174\/1389450116666150804110412","article-title":"Targeting Interferon Regulatory Factor for Cardiometabolic Diseases: Opportunities and Challenges","volume":"18","author":"Zhang","year":"2017","journal-title":"Curr. Drug Targets"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Huang, J., Wang, J., Chen, H., Guo, F., and Yuan, X. (2026). The role of interferon regulatory factors in atherosclerosis: From cell type-specific mechanisms to therapeutic strategies. Front. Cell Dev. Biol., 14.","DOI":"10.3389\/fcell.2026.1795987"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Xie, J., An, X., Gao, Y., Du, K., Chen, H., Zhang, J., Chen, T., and Hou, J. (2026). Interferon regulatory factors: The next prospective targets for tissue ischemia\u2013reperfusion injury?. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1782849"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nrneph.2017.51","article-title":"The immunology of atherosclerosis","volume":"13","author":"Gistera","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1161\/CIRCRESAHA.114.302721","article-title":"Mechanisms of plaque formation and rupture","volume":"114","author":"Bentzon","year":"2014","journal-title":"Circ. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/nri2675","article-title":"Macrophage death and defective inflammation resolution in atherosclerosis","volume":"10","author":"Tabas","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nri2156","article-title":"Getting to the site of inflammation: The leukocyte adhesion cascade updated","volume":"7","author":"Ley","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/jcmm.12689","article-title":"Macrophage-mediated cholesterol handling in atherosclerosis","volume":"20","author":"Chistiakov","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1152\/physrev.00041.2003","article-title":"Molecular regulation of vascular smooth muscle cell differentiation in development and disease","volume":"84","author":"Owens","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1161\/hc0902.104353","article-title":"Inflammation and atherosclerosis","volume":"105","author":"Libby","year":"2002","journal-title":"Circulation"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1038\/nature08938","article-title":"NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals","volume":"464","author":"Duewell","year":"2010","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1161\/ATVBAHA.108.179739","article-title":"Concept of vulnerable\/unstable plaque","volume":"30","author":"Finn","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_41","first-page":"377","article-title":"11-dehydro thromboxane B2 levels after percutaneous transluminal angioplasty in patients with peripheral arterial occlusive disease during a one year follow-up period","volume":"67","author":"Maga","year":"2016","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"147","DOI":"10.5603\/AA.2022.0013","article-title":"Leukotrienes in the atherosclerotic cardiovascular diseases\u2014A systematic review","volume":"28","author":"Kaszuba","year":"2022","journal-title":"Acta Angiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1242\/jcs.00963","article-title":"The JAK\/STAT signaling pathway","volume":"117","author":"Rawlings","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"LPS\/TLR4 signal transduction pathway","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/cr.2011.13","article-title":"NF-kappaB in immunobiology","volume":"21","author":"Hayden","year":"2011","journal-title":"Cell Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nm.3893","article-title":"Inflammasomes: Mechanism of action, role in disease, and therapeutics","volume":"21","author":"Guo","year":"2015","journal-title":"Nat. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1161\/CIRCRESAHA.108.188318","article-title":"Autophagy in atherosclerosis: A cell survival and death phenomenon with therapeutic potential","volume":"104","author":"Martinet","year":"2009","journal-title":"Circ. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"S382","DOI":"10.1194\/jlr.R800032-JLR200","article-title":"Mechanisms and consequences of macrophage apoptosis in atherosclerosis","volume":"50","author":"Seimon","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhao, Y., Ye, T., Yang, L., Shen, Y., and Li, H. (2021). Ferroptosis Signaling and Regulators in Atherosclerosis. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.809457"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1189\/jlb.0209115","article-title":"Mechanisms and consequences of efferocytosis in advanced atherosclerosis","volume":"86","author":"Thorp","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1161\/01.ATV.0000054658.91146.64","article-title":"Cholesteryl ester transfer protein: A novel target for raising HDL and inhibiting atherosclerosis","volume":"23","author":"Barter","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1194\/jlr.R400010-JLR200","article-title":"PPAR- and LXR-dependent pathways controlling lipid metabolism and the development of atherosclerosis","volume":"45","author":"Li","year":"2004","journal-title":"J. Lipid Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1016\/j.jacc.2013.11.002","article-title":"2013 ACC\/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines","volume":"63","author":"Stone","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.pcad.2016.07.011","article-title":"Nonstatins and Proprotein Convertase Subtilisin\/Kexin Type 9 (PCSK9) Inhibitors: Role in Non-Familial Hypercholesterolemia","volume":"59","author":"Robinson","year":"2016","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/S0140-6736(09)60697-8","article-title":"Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: A meta-analysis of randomised controlled trials","volume":"373","author":"Ray","year":"2009","journal-title":"Lancet"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1001\/jama.2024.24017","article-title":"Oral Muvalaplin for Lowering of Lipoprotein(a)","volume":"333","author":"Nicholls","year":"2025","journal-title":"JAMA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1152\/physrev.00012.2005","article-title":"Signaling mechanisms regulating endothelial permeability","volume":"86","author":"Mehta","year":"2006","journal-title":"Physiol. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.1161\/ATVBAHA.107.149179","article-title":"Vascular adhesion molecules in atherosclerosis","volume":"27","author":"Galkina","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.molmed.2017.02.004","article-title":"Epigenetics of Atherosclerosis: Emerging Mechanisms and Methods","volume":"23","author":"Khyzha","year":"2017","journal-title":"Trends Mol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Haemmig, S., Simion, V., and Feinberg, M.W. (2018). Long Non-Coding RNAs in Vascular Inflammation. Front. Cardiovasc. Med., 5.","DOI":"10.3389\/fcvm.2018.00022"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1001\/jama.288.20.2569","article-title":"Optimal diets for prevention of coronary heart disease","volume":"288","author":"Hu","year":"2002","journal-title":"JAMA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.1161\/01.cir.0000437740.48606.d1","article-title":"2013 AHA\/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk","volume":"129","author":"Eckel","year":"2014","journal-title":"Circulation"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1093\/eurheartj\/ehw106","article-title":"2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR)","volume":"37","author":"Piepoli","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Galvan-Pena, S., and O\u2019Neill, L.A. (2014). Metabolic reprograming in macrophage polarization. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00420"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1016\/j.celrep.2016.07.060","article-title":"IRF5 and IRF5 Disease-Risk Variants Increase Glycolysis and Human M1 Macrophage Polarization by Regulating Proximal Signaling and Akt2 Activation","volume":"16","author":"Hedl","year":"2016","journal-title":"Cell Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s40164-025-00612-z","article-title":"IRF1 is a core transcriptional regulatory circuitry member promoting AML progression by regulating lipid metabolism","volume":"14","author":"Zhang","year":"2025","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/nri2634","article-title":"Transcriptional control of the inflammatory response","volume":"9","author":"Medzhitov","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nrg.2016.59","article-title":"The molecular hallmarks of epigenetic control","volume":"17","author":"Allis","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.lfs.2010.07.012","article-title":"C-reactive protein triggers inflammatory responses partly via TLR4\/IRF3\/NF-kappaB signaling pathway in rat vascular smooth muscle cells","volume":"87","author":"Liu","year":"2010","journal-title":"Life Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.7150\/thno.87201","article-title":"Re-analysis of single-cell transcriptomics reveals a critical role of macrophage-like smooth muscle cells in advanced atherosclerotic plaque","volume":"14","author":"Gong","year":"2024","journal-title":"Theranostics"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"pbaf039","DOI":"10.1093\/pcmedi\/pbaf039","article-title":"IRF7 orchestrates maladaptive smooth muscle cell phenotype switching in atherosclerosis","volume":"9","author":"Cai","year":"2026","journal-title":"Precis. Clin. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1161\/01.CIR.101.16.1982","article-title":"Nitric oxide modulates expression of cell cycle regulatory proteins: A cytostatic strategy for inhibition of human vascular smooth muscle cell proliferation","volume":"101","author":"Tanner","year":"2000","journal-title":"Circulation"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"C144","DOI":"10.1152\/ajpcell.2002.282.1.C144","article-title":"Molecular mechanisms of iNOS induction by IL-1 beta and IFN-gamma in rat aortic smooth muscle cells","volume":"282","author":"Teng","year":"2002","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.canlet.2011.12.027","article-title":"Interferon Regulatory Factor 1 (IRF-1) induces p21(WAF1\/CIP1) dependent cell cycle arrest and p21(WAF1\/CIP1) independent modulation of survivin in cancer cells","volume":"319","author":"Armstrong","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"933","DOI":"10.18632\/aging.202204","article-title":"IRF-1 contributes to the pathological phenotype of VSMCs during atherogenesis by increasing CCL19 transcription","volume":"13","author":"Shen","year":"2020","journal-title":"Aging"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/s41419-023-05821-0","article-title":"Thymidine phosphorylase facilitates retinoic acid inducible gene-I induced endothelial dysfunction","volume":"14","author":"Baris","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s10557-023-07523-3","article-title":"IL-33 Suppresses the Progression of Atherosclerosis via the ERK1\/2-IRF1-VCAM-1 Pathway","volume":"38","author":"Qian","year":"2024","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1165\/rcmb.2020-0524OC","article-title":"Nur77 Attenuates Inflammasome Activation by Inhibiting Caspase-1 Expression in Pulmonary Vascular Endothelial Cells","volume":"65","author":"Ding","year":"2021","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e2004162","DOI":"10.1002\/advs.202004162","article-title":"The Transcription Factor SUB1 Is a Master Regulator of the Macrophage TLR Response in Atherosclerosis","volume":"8","author":"Huang","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2917128","DOI":"10.1155\/2019\/2917128","article-title":"IFN Regulatory Factor 1 Mediates Macrophage Pyroptosis Induced by Oxidized Low-Density Lipoprotein in Patients with Acute Coronary Syndrome","volume":"2019","author":"Guo","year":"2019","journal-title":"Mediat. Inflamm."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s12265-024-10556-0","article-title":"AIM2 Deficiency Alleviates Cardiac Inflammation and Hypertrophy in HFD\/STZ-Induced Diabetic Mice by Inhibiting the NLRC4\/IRF1 Signaling Pathway","volume":"18","author":"Wu","year":"2025","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Zhu, X., Guo, Q., Zou, J., Wang, B., Zhang, Z., Wei, R., Zhao, L., Zhang, Y., Chu, C., and Fu, X. (2021). MiR-19a-3p Suppresses M1 Macrophage Polarization by Inhibiting STAT1\/IRF1 Pathway. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.614044"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1016\/j.jacc.2015.02.032","article-title":"Evolving therapies for myocardial ischemia\/reperfusion injury","volume":"65","author":"Ibanez","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"105141","DOI":"10.1016\/j.jbc.2023.105141","article-title":"Immune regulator IRF1 contributes to ZBP1-, AIM2-, RIPK1-, and NLRP12-PANoptosome activation and inflammatory cell death (PANoptosis)","volume":"299","author":"Sharma","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.4049\/jimmunol.1701538","article-title":"IRF1 Is a Transcriptional Regulator of ZBP1 Promoting NLRP3 Inflammasome Activation and Cell Death during Influenza Virus Infection","volume":"200","author":"Kuriakose","year":"2018","journal-title":"J. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S1074-7613(02)00390-4","article-title":"IRF3 mediates a TLR3\/TLR4-specific antiviral gene program","volume":"17","author":"Doyle","year":"2002","journal-title":"Immunity"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ni921","article-title":"IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway","volume":"4","author":"Fitzgerald","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1042\/BCJ20160992","article-title":"Identification of TBK1 complexes required for the phosphorylation of IRF3 and the production of interferon beta","volume":"474","author":"Bakshi","year":"2017","journal-title":"Biochem. J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/nature12640","article-title":"Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP","volume":"503","author":"Ablasser","year":"2013","journal-title":"Nature"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"16470","DOI":"10.1038\/s41598-023-43848-7","article-title":"A possible role for proinflammatory activation via cGAS-STING pathway in atherosclerosis induced by accumulation of DNA double-strand breaks","volume":"13","author":"Sakai","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4765","DOI":"10.1016\/j.apsb.2023.08.015","article-title":"Non-canonical STING-PERK pathway dependent epigenetic regulation of vascular endothelial dysfunction via integrating IRF3 and NF-kappaB in inflammatory response","volume":"13","author":"Li","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1161\/HYPERTENSIONAHA.116.08486","article-title":"Ablation of Interferon Regulatory Factor 3 Promotes the Stability of Atherosclerotic Plaques","volume":"69","author":"Okon","year":"2017","journal-title":"Hypertension"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e201909081","DOI":"10.1083\/jcb.201909081","article-title":"VE-cadherin endocytosis controls vascular integrity and patterning during development","volume":"219","author":"Isaacson","year":"2020","journal-title":"J. Cell Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.bcmd.2005.12.008","article-title":"Role of tissue factor in hemostasis and thrombosis","volume":"36","author":"Mackman","year":"2006","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s00281-011-0282-8","article-title":"Thrombomodulin and its role in inflammation","volume":"34","author":"Conway","year":"2012","journal-title":"Semin. Immunopathol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1161\/HYPERTENSIONAHA.116.08395","article-title":"Ablation of Interferon Regulatory Factor 3 Protects Against Atherosclerosis in Apolipoprotein E-Deficient Mice","volume":"69","author":"Liu","year":"2017","journal-title":"Hypertension"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Majoros, A., Platanitis, E., Kernbauer-Holzl, E., Rosebrock, F., Muller, M., and Decker, T. (2017). Canonical and Non-Canonical Aspects of JAK-STAT Signaling: Lessons from Interferons for Cytokine Responses. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00029"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Michalska, A., Blaszczyk, K., Wesoly, J., and Bluyssen, H.A.R. (2018). A Positive Feedback Amplifier Circuit That Regulates Interferon (IFN)-Stimulated Gene Expression and Controls Type I and Type II IFN Responses. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01135"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1038\/ni.1920","article-title":"The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection","volume":"11","author":"Satoh","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/ni.1990","article-title":"IRF5 promotes inflammatory macrophage polarization and TH1\u2013TH17 responses","volume":"12","author":"Krausgruber","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"17005","DOI":"10.1074\/jbc.M412584200","article-title":"The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling","volume":"280","author":"Schoenemeyer","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nature03308","article-title":"Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors","volume":"434","author":"Takaoka","year":"2005","journal-title":"Nature"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"101250","DOI":"10.1016\/j.molmet.2021.101250","article-title":"Myeloid cell-specific Irf5 deficiency stabilizes atherosclerotic plaques in Apoe(-\/-) mice","volume":"53","author":"Leipner","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/nature05894","article-title":"Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance","volume":"447","author":"Odegaard","year":"2007","journal-title":"Nature"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"30288","DOI":"10.1074\/jbc.M109.045104","article-title":"Uptake of oxidized low density lipoprotein by CD36 occurs by an actin-dependent pathway distinct from macropinocytosis","volume":"284","author":"Collins","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/ni.2622","article-title":"The nuclear receptor LXRalpha controls the functional specialization of splenic macrophages","volume":"14","author":"Gonzalez","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"eaar3721","DOI":"10.1126\/scisignal.aar3721","article-title":"MerTK signaling in macrophages promotes the synthesis of inflammation resolution mediators by suppressing CaMKII activity","volume":"11","author":"Cai","year":"2018","journal-title":"Sci. Signal."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1161\/CIRCRESAHA.117.312509","article-title":"Single-Cell RNA-Seq Reveals the Transcriptional Landscape and Heterogeneity of Aortic Macrophages in Murine Atherosclerosis","volume":"122","author":"Cochain","year":"2018","journal-title":"Circ. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e2416238","DOI":"10.1002\/advs.202416238","article-title":"IRF8 Drives Conventional Type 1 Dendritic Cell Differentiation and CD8(+) T Cell Activation to Aggravate Abdominal Aortic Aneurysm Development","volume":"12","author":"Yuan","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1084\/jem.20151764","article-title":"The macrophage IRF8\/IRF1 regulome is required for protection against infections and is associated with chronic inflammation","volume":"213","author":"Langlais","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Britsch, S., Langer, H., Duerschmied, D., and Becher, T. (2024). The Evolving Role of Dendritic Cells in Atherosclerosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042450"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"4666","DOI":"10.1038\/s44318-025-00482-5","article-title":"cGAS-STING are responsible for premature aging of telomerase-deficient zebrafish","volume":"44","author":"Serifoglu","year":"2025","journal-title":"EMBO J."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.7150\/ijbs.90459","article-title":"WTAP Mediated N6-methyladenosine RNA Modification of ELF3 Drives Cellular Senescence by Upregulating IRF8","volume":"20","author":"Zhou","year":"2024","journal-title":"Int. J. Biol. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1161\/CIRCRESAHA.118.312713","article-title":"Deletion of IRF8 (Interferon Regulatory Factor 8)-Dependent Dendritic Cells Abrogates Proatherogenic Adaptive Immunity","volume":"122","author":"Clement","year":"2018","journal-title":"Circ. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e155552","DOI":"10.1172\/jci.insight.155552","article-title":"The TBK1\/IKKepsilon inhibitor amlexanox improves dyslipidemia and prevents atherosclerosis","volume":"7","author":"Zhao","year":"2022","journal-title":"JCI Insight"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1161\/ATVBAHA.117.309017","article-title":"STING-IRF3 Triggers Endothelial Inflammation in Response to Free Fatty Acid-Induced Mitochondrial Damage in Diet-Induced Obesity","volume":"37","author":"Mao","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s10741-018-09764-z","article-title":"Curcumin as a potential modulator of M1 and M2 macrophages: New insights in atherosclerosis therapy","volume":"24","author":"Abdollahi","year":"2019","journal-title":"Heart Fail. Rev."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"77635","DOI":"10.18632\/oncotarget.12749","article-title":"Bcr-abl regulates Stat5 through Shp2, the interferon consensus sequence binding protein (Icsbp\/Irf8), growth arrest specific 2 (Gas2) and calpain","volume":"7","author":"Hjort","year":"2016","journal-title":"Oncotarget"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Bartusik-Aebisher, D., Podgorski, R., Serafin, I., and Aebisher, D. (2025). Targeted and Biomimetic Nanoparticles for Atherosclerosis Therapy: A Review of Emerging Strategies. Biomedicines, 13.","DOI":"10.3390\/biomedicines13071720"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.2147\/IJN.S503774","article-title":"Golden Tandem of Photothermal Ablation and Simultaneous Anti-Inflammation in One Nanoparticle for Activated Macrophage-Targeted Atherosclerosis Treatment","volume":"20","author":"Lu","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"40480","DOI":"10.1038\/s41598-025-24447-0","article-title":"Apigenin-loaded exosome-like vesicles suppress triple-negative breast cancer by modulating miR-155\/SOCS1\/VHL, miR-146a\/IRAK1\/TRAF6 and reactivating STING\/BRCA1: Department of Biology, QaS.C., Islamic Azad University, Qaemshahr, Iran","volume":"15","author":"Dehpour","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1093\/eurheartj\/ehab920","article-title":"Interferon regulatory factor-5-dependent CD11c+ macrophages contribute to the formation of rupture-prone atherosclerotic plaques","volume":"43","author":"Edsfeldt","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41392-024-01980-4","article-title":"The multiple roles of interferon regulatory factor family in health and disease","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e04990","DOI":"10.1002\/advs.202504990","article-title":"Nanoparticle Drug Delivery Systems for Atherosclerosis: Precision Targeting, Inflammatory Modulation, and Plaque Stabilization","volume":"12","author":"Zhang","year":"2025","journal-title":"Adv. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7647\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:27:45Z","timestamp":1787891265000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":127,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177647"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177647","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]}}}