{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:41:47Z","timestamp":1789486907001,"version":"build-2803163510"},"reference-count":107,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["25-75-10016"],"award-info":[{"award-number":["25-75-10016"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["25-75-10016"],"award-info":[{"award-number":["25-75-10016"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Atherosclerosis is a chronic immune\u2013inflammatory disease of the arterial wall in which antigen-presenting cells (dendritic cells, macrophages and B cells) present locally generated antigens, such as oxidized low-density lipoprotein, to plaque-infiltrating T cells. Full T-cell activation requires costimulation through the B7 family ligands CD80 (B7-1) and CD86 (B7-2), which engage CD28 to activate T cells and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to restrain them. Although long considered functionally redundant, CD80 and CD86 are now known to be structurally and mechanistically distinct, differing in receptor affinity, susceptibility to CTLA-4-mediated trans-endocytosis, capacity to cis-heterodimerize with programmed death-ligand 1, and dependence relationships with regulatory versus effector T cells. In atherosclerosis, CD80 is expressed by lesional dendritic cells, macrophages, foam cells, B cells and, under inflammatory conditions, vascular endothelial and smooth muscle cells, with expression levels correlating with plaque vulnerability in humans. Genetic deletion, CTLA-4-Ig-based pharmacological blockade and selective small-molecule antagonism in preclinical models generally converge on a proatherogenic role for CD80\/CD86-dependent costimulation, although combined genetic deletion of CD80 and CD86 has also been reported to paradoxically enhance early lesion formation in some contexts, while augmented CTLA-4-mediated coinhibition is atheroprotective\u2014a balance corroborated by the accelerated atherosclerosis and cardiovascular toxicity observed with checkpoint-inhibitor cancer immunotherapy. Molecular imaging agents targeting CD80\/CD86, repurposed CTLA-4-Ig biologics such as abatacept, and antigen-specific tolerogenic dendritic cell strategies together constitute an emerging translational pipeline. To our knowledge, this is the first review to integrate CD80\u2019s structural and receptor pharmacology with its cellular sources in the plaque, preclinical genetic and pharmacological evidence, human plaque and biomarker data, molecular imaging approaches, and checkpoint inhibitor-associated cardiovascular toxicity within a single translational framework. This review synthesizes the structural biology, cellular sources, preclinical genetics, human plaque and biomarker data, and therapeutic and diagnostic implications of CD80 as an immune mediator and candidate therapeutic target in atherosclerosis.<\/jats:p>","DOI":"10.3390\/ijms27188215","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:33:42Z","timestamp":1789479222000},"page":"8215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CD80 as an Important Immune Mediator and Therapeutic Target in Atherosclerosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Alexander","family":"Blagov","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Genetic Modeling of Inflammaging, Institute of General Pathology and Pathophysiology, 8, Baltiiskaya Street, 125315 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6499-3908","authenticated-orcid":false,"given":"Aleksey","family":"Vatlin","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetic Modeling of Inflammaging, Institute of General Pathology and Pathophysiology, 8, Baltiiskaya Street, 125315 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3596-5470","authenticated-orcid":false,"given":"Daria","family":"Borodko","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetic Modeling of Inflammaging, Institute of General Pathology and Pathophysiology, 8, Baltiiskaya Street, 125315 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Maksaeva","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetic Modeling of Inflammaging, Institute of General Pathology and Pathophysiology, 8, Baltiiskaya Street, 125315 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","unstructured":"GBD 2023 Cardiovascular Diseases Collaborators (2025). Global, Regional, and National Burden of Cardiovascular Diseases and Risk Factors in 204 Countries and Territories, 1990\u20132023. J. Am. Coll. Cardiol., 86, 22."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1093\/eurjpc\/zwae281","article-title":"Global burden of cardiovascular diseases: Projections from 2025 to 2050","volume":"32","author":"Chong","year":"2024","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"GBD 2021 China Collaborators (2025). The epidemiology and burden of atherosclerotic cardiovascular disease in China from 1990 to 2021: Findings from the global burden of disease 2021. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1470021"},{"key":"ref_4","unstructured":"(2025). GBD 2021 Risk Factors Collaborators. Global, regional, and national burden of cardiovascular disease attributable to high body mass index from 1990 to 2021 and projection to 2045. Front. Endocrinol., 16."},{"key":"ref_5","unstructured":"(2025). GBD 2021 Causes of Death Collaborators. Trends and predictive research on the global burden of ischemic heart disease from 1990 to 2021: An analysis of the Global Burden of Disease study 2021. Front. Public Health, 13."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.7150\/ijms.94570","article-title":"The role of immune cells in different stages of atherosclerosis","volume":"21","author":"He","year":"2024","journal-title":"Int. J. Med. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Liu, T., Chen, Y., Hou, L., Yu, Y., Ma, D., Jiang, T., and Zhao, G. (2024). Immune cell-mediated features of atherosclerosis. Front. Cardiovasc. Med., 11.","DOI":"10.3389\/fcvm.2024.1450737"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1161\/ATVBAHA.124.319397","article-title":"Century of Milestones and Breakthroughs Related to the Immune Mechanisms of Atherosclerosis","volume":"44","author":"Mallat","year":"2024","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nature10146","article-title":"Progress and challenges in translating the biology of atherosclerosis","volume":"473","author":"Libby","year":"2011","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.it.2011.07.001","article-title":"How dendritic cells shape atherosclerosis","volume":"32","author":"Koltsova","year":"2011","journal-title":"Trends Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/labinvest.2010.94","article-title":"Dendritic cells and their role in atherogenesis","volume":"90","author":"Bobryshev","year":"2010","journal-title":"Lab. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.jacc.2021.11.048","article-title":"Immune Checkpoint Therapies and Atherosclerosis: Mechanisms and Clinical Implications: JACC State-of-the-Art Review","volume":"79","author":"Vuong","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.4049\/jimmunol.143.8.2714","article-title":"B7, a new member of the Ig superfamily with unique expression on activated and neoplastic B cells","volume":"143","author":"Freeman","year":"1989","journal-title":"J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1084\/jem.173.3.721","article-title":"Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation","volume":"173","author":"Linsley","year":"1991","journal-title":"J. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1126\/science.7694363","article-title":"Cloning of B7-2: A CTLA-4 counter-receptor that costimulates human T cell proliferation","volume":"262","author":"Freeman","year":"1993","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1146\/annurev.immunol.23.021704.115611","article-title":"The B7 family revisited","volume":"23","author":"Greenwald","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"97","DOI":"10.4049\/jimmunol.154.1.97","article-title":"CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTL","volume":"154","author":"Lanier","year":"1995","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/0167-5699(94)90080-9","article-title":"The B7 and CD28 receptor families","volume":"15","author":"June","year":"1994","journal-title":"Immunol. Today"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/1074-7613(94)90071-X","article-title":"CTLA-4 can function as a negative regulator of T cell activation","volume":"1","author":"Walunas","year":"1994","journal-title":"Immunity"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1084\/jem.182.2.459","article-title":"CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation","volume":"182","author":"Krummel","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/s41590-022-01289-w","article-title":"Differences in CD80 and CD86 transendocytosis reveal CD86 as a key target for CTLA-4 immune regulation","volume":"23","author":"Kennedy","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.immuni.2019.11.003","article-title":"PD-L1:CD80 Cis-Heterodimer Triggers the Co-stimulatory Receptor CD28 While Repressing the Inhibitory PD-1 and CTLA-4 Pathways","volume":"51","author":"Zhao","year":"2019","journal-title":"Immunity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1126\/science.aav7062","article-title":"Restriction of PD-1 function by cis-PD-L1\/CD80 interactions is required for optimal T cell responses","volume":"364","author":"Sugiura","year":"2019","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1038\/s44161-024-00563-4","article-title":"Immune checkpoint landscape of human atherosclerosis and influence of cardiometabolic factors","volume":"3","author":"Das","year":"2024","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1161\/01.CIR.0000127121.16815.F1","article-title":"B7-1\/B7-2 costimulation regulates plaque antigen-specific T-cell responses and atherogenesis in low-density lipoprotein receptor-deficient mice","volume":"109","author":"Buono","year":"2004","journal-title":"Circulation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s11936-023-01024-0","article-title":"Immunotherapy-Associated Atherosclerosis: A Comprehensive Review of Recent Findings and Implications for Future Research","volume":"25","author":"Chan","year":"2023","journal-title":"Curr. Treat. Options Cardiovasc. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1097\/MOL.0000000000000538","article-title":"Cardiovascular Oncology: Exploring the Effects of Targeted Cancer Therapies on Atherosclerosis","volume":"29","author":"Seijkens","year":"2018","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S1074-7613(00)80158-2","article-title":"Structure and dimerization of a soluble form of B7-1","volume":"12","author":"Ikemizu","year":"2000","journal-title":"Immunity"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/35069118","article-title":"Crystal structure of the B7-1\/CTLA-4 complex that inhibits human immune responses","volume":"410","author":"Stamper","year":"2001","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1073\/pnas.252771499","article-title":"Crystal structure of the receptor-binding domain of human B7-2: Insights into organization and signaling","volume":"100","author":"Zhang","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/jlb.64.6.803","article-title":"Costimulatory molecules CD80 and CD86 in the rat: Tissue distribution and expression by antigen-presenting cells","volume":"64","author":"Damoiseaux","year":"1998","journal-title":"J. Leukoc. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1126\/science.1202947","article-title":"Trans-endocytosis of CD80 and CD86: A molecular basis for the cell-extrinsic function of CTLA-4","volume":"332","author":"Qureshi","year":"2011","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e013757","DOI":"10.1161\/JAHA.119.013757","article-title":"Immune Checkpoint Inhibitor Myocarditis: Pathophysiological Characteristics, Diagnosis, and Treatment","volume":"9","author":"Palaskas","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Halliday, N., Williams, C., Kennedy, A., Waters, E., Pesenacker, A.M., Soskic, B., Hinze, C., Hou, T.Z., Rowshanravan, B., and Janman, D. (2020). CD86 Is a Selective CD28 Ligand Supporting FoxP3+ Regulatory T Cell Homeostasis in the Presence of High Levels of CTLA-4. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.600000"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Soskic, B., Jeffery, L.E., Kennedy, A., Gardner, D.H., Hou, T.Z., Halliday, N., Williams, C., Janman, D., Rowshanravan, B., and Hirschfield, G.M. (2020). CD80 on Human T Cells Is Associated with FoxP3 Expression and Supports Treg Homeostasis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.577655"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5894","DOI":"10.4049\/jimmunol.1401752","article-title":"CD28-CD80 interactions control regulatory T cell motility and immunological synapse formation","volume":"193","author":"Thauland","year":"2014","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Dilek, N., Poirier, N., Hulin, P., Coulon, F., Mary, C., Ville, S., Vie, H., Cl\u00e9menceau, B., Blancho, G., and Vanhove, B. (2013). Targeting CD28, CTLA-4 and PD-L1 Costimulation Differentially Controls Immune Synapses and Function of Human Regulatory and Conventional T-Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083139"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e202551771","DOI":"10.1002\/eji.202551771","article-title":"Treg Control of CD80\/CD86 Expression Mediates Immune System Homeostasis","volume":"55","author":"Kim","year":"2025","journal-title":"Eur. J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pinto, B.F., Medeiros, N.I., Teixeira-Carvalho, A., Fiuza, J.A., Eloi-Santos, S.M., Nunes, M.C.P., Silva, S.A., Fontes-Cal, T.C.M., Belchior-Bezerra, M., and Dutra, W.O. (2022). Modulation of Regulatory T Cells Activity by Distinct CD80 and CD86 Interactions with CD28\/CTLA-4 in Chagas Cardiomyopathy. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.750876"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"eaba7107","DOI":"10.1126\/sciimmunol.aba7107","article-title":"Cis-interactions Make Immune Checkpoint Blockade More Trans-parent","volume":"5","author":"Khatwani","year":"2020","journal-title":"Sci. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.immuni.2007.05.016","article-title":"Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses","volume":"27","author":"Butte","year":"2007","journal-title":"Immunity"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"(2019). PD-L1\/CD80 cis Interactions Disrupt PD-L1-PD-1 Binding and Promote T-cell Function. Cancer Discov., 9, OF10.","DOI":"10.1158\/2159-8290.CD-RW2019-075"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e111556","DOI":"10.15252\/embj.2022111556","article-title":"The CTLA-4 immune checkpoint protein regulates PD-L1:PD-1 interaction via transendocytosis of its ligand CD80","volume":"42","author":"Kennedy","year":"2023","journal-title":"EMBO J."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Butcher, M.J., and Galkina, E.V. (2012). Phenotypic and Functional Heterogeneity of Macrophages and Dendritic Cell Subsets in the Healthy and Atherosclerosis-Prone Aorta. Front. Physiol., 3.","DOI":"10.3389\/fphys.2012.00044"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13550-015-0157-4","article-title":"Preclinical imaging of the co-stimulatory molecules CD80 and CD86 with indium-111-labeled belatacept in atherosclerosis","volume":"6","author":"Meletta","year":"2016","journal-title":"EJNMMI Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1476-511X-10-1","article-title":"Different responses to oxidized low-density lipoproteins in human polarized macrophages","volume":"10","author":"Hirose","year":"2011","journal-title":"Lipids Health Dis."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yu, H., Josi, R.R., Khanna, A., and Khismatullin, D.B. (2025). Low-Density Lipoproteins Induce a Pro-Inflammatory, Chemotactic Mox-like Phenotype in THP-1-Derived Human Macrophages. Cells, 15.","DOI":"10.3390\/cells15010055"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"110338","DOI":"10.1016\/j.intimp.2023.110338","article-title":"Oxidized low-density lipoprotein regulates macrophage polarization in atherosclerosis","volume":"120","author":"He","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.yexmp.2003.12.001","article-title":"Evidence for the involvement of T cell costimulation through the B-7\/CD28 pathway in atherosclerotic plaques from apolipoprotein E knockout mice","volume":"76","author":"Afek","year":"2004","journal-title":"Exp. Mol. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0021-9150(97)00135-4","article-title":"Costimulatory molecules in human atherosclerotic plaques: An indication of antigen specific T lymphocyte activation","volume":"133","author":"Hirsch","year":"1997","journal-title":"Atherosclerosis"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Raggi, F., Pelassa, S., Pierobon, D., Penco, F., Gattorno, M., Novelli, F., Eva, A., Varesio, L., Giovarelli, M., and Bosco, M.C. (2017). Regulation of Human Macrophage M1-M2 Polarization Balance by Hypoxia and the Triggering Receptor Expressed on Myeloid Cells-1. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01097"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"14362","DOI":"10.1038\/s41598-020-71110-x","article-title":"CD163+ macrophages are associated with a vulnerable plaque phenotype in human carotid plaques","volume":"10","author":"Bengtsson","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e71","DOI":"10.1161\/ATVBAHA.117.310678","article-title":"Follicular B Cells Promote Atherosclerosis via T Cell-Mediated Differentiation Into Plasma Cells and Secreting Pathogenic Immunoglobulin G","volume":"38","author":"Tay","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_55","first-page":"2544","article-title":"Humoral immunity in atherosclerosis and myocardial infarction: From B cells to antibodies","volume":"117","author":"Porsch","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1084\/jem.177.4.925","article-title":"Activated T cells induce expression of B7\/BB1 on normal or leukemic B cells through a CD40-dependent signal","volume":"177","author":"Ranheim","year":"1993","journal-title":"J. Exp. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jaut.2019.04.016","article-title":"Abatacept modulates CD80 and CD86 expression and memory formation in human B-cells","volume":"101","author":"Lorenzetti","year":"2019","journal-title":"J. Autoimmun."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Sch\u00e4fer, S., and Zernecke, A. (2020). CD8+ T Cells in Atherosclerosis. Cells, 10.","DOI":"10.3390\/cells10010037"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Annink, M.E., Kraaijenhof, J.M., Stroes, E.S.G., and Kroon, J. (2024). Moving from lipids to leukocytes: Inflammation and immune cells in atherosclerosis. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1446758"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41569-020-0352-5","article-title":"T cell subsets and functions in atherosclerosis","volume":"17","author":"Saigusa","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"15414","DOI":"10.1038\/srep15414","article-title":"Ablation of CD8\u03b1+ dendritic cell mediated cross-presentation does not impact atherosclerosis in hyperlipidemic mice","volume":"5","author":"Legein","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1084\/jem.180.4.1263","article-title":"Activation of human dendritic cells through CD40 cross-linking","volume":"180","author":"Caux","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"13967","DOI":"10.1073\/pnas.93.24.13967","article-title":"Costimulatory function and expression of CD40 ligand, CD80, and CD86 in vascularized murine cardiac allograft rejection","volume":"93","author":"Hancock","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"69","DOI":"10.29245\/2578-3009\/2018\/3.1144","article-title":"T Cells in Atherosclerosis in Ldlr\u2212\/\u2212 and Apoe\u2212\/\u2212 Mice","volume":"2","author":"Getz","year":"2018","journal-title":"J. Immunol. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Lichtman, A.H. (2012). T Cell Costimulatory and Coinhibitory Pathways in Vascular Inflammatory Diseases. Front. Physiol., 3.","DOI":"10.3389\/fphys.2012.00018"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.immuni.2013.06.009","article-title":"Immune effector mechanisms implicated in atherosclerosis: From mice to humans","volume":"38","author":"Libby","year":"2013","journal-title":"Immunity"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/j.ijcard.2012.12.085","article-title":"T-cell co-stimulation by CD28-CD80\/86 and its negative regulator CTLA-4 strongly influence accelerated atherosclerosis development","volume":"168","author":"Ewing","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S0002-9440(10)64559-2","article-title":"Association of B7-1 co-stimulation with the development of graft arterial disease: Studies using mice lacking B7-1, B7-2, or B7-1\/B7-2","volume":"157","author":"Furukawa","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1093\/cvr\/cvs330","article-title":"CTLA4-IgG ameliorates homocysteine-accelerated atherosclerosis by inhibiting T-cell overactivation in apoE(\u2212\/\u2212) mice","volume":"97","author":"Ma","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00395-024-01070-0","article-title":"Preclinical models of cardiotoxicity from immune checkpoint inhibitor therapy","volume":"120","author":"Buehning","year":"2025","journal-title":"Basic. Res. Cardiol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Poels, K., van Leent, M.M.T., Reiche, M.E., Kusters, P.J.H., Huveneers, S., de Winther, M.P.J., Mulder, W.J.M., Lutgens, E., and Seijkens, T.T.P. (2020). Antibody-Mediated Inhibition of CTLA4 Aggravates Atherosclerotic Plaque Inflammation and Progression in Hyperlipidemic Mice. Cells, 9.","DOI":"10.3390\/cells9091987"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"119147","DOI":"10.1016\/j.atherosclerosis.2025.119147","article-title":"Immune checkpoint inhibitors: Unravelling atherosclerotic cardiovascular risk","volume":"403","author":"Gray","year":"2025","journal-title":"Atherosclerosis"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Nardin, S., Ruffilli, B., Costantini, P., Mollace, R., Taglialatela, I., Pagnesi, M., Chiarito, M., Soldato, D., Cao, D., and Conte, B. (2025). Navigating Cardiotoxicity in Immune Checkpoint Inhibitors: From Diagnosis to Long-Term Management. J. Cardiovasc. Dev. Dis., 12.","DOI":"10.3390\/jcdd12070270"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"447","DOI":"10.2147\/DDDT.S59594","article-title":"Inhibition of B7-1 (CD80) by RhuDex\u00ae reduces lipopolysaccharide-mediated inflammation in human atherosclerotic lesions","volume":"8","author":"Doesch","year":"2014","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Chistiakov, D.A., Sobenin, I.A., Orekhov, A.N., and Bobryshev, Y.V. (2014). Dendritic cells in atherosclerotic inflammation: The complexity of functions and the peculiarities of pathophysiological effects. Front. Physiol., 5.","DOI":"10.3389\/fphys.2014.00196"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1161\/CIRCULATIONAHA.110.973222","article-title":"Immunotherapy with tolerogenic apolipoprotein B-100-loaded dendritic cells attenuates atherosclerosis in hypercholesterolemic mice","volume":"123","author":"Hermansson","year":"2011","journal-title":"Circulation"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.apsb.2024.12.029","article-title":"Dendritic cells immunotargeted therapy for atherosclerosis","volume":"15","author":"Li","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Pellerin, L., Chen, P., Gregori, S., Hernandez-Hoyos, G., Bacchetta, R., and Roncarolo, M.G. (2018). APVO210: A Bispecific Anti-CD86-IL-10 Fusion Protein (ADAPTIR\u2122) to Induce Antigen-Specific T Regulatory Type 1 Cells. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00881"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e003976","DOI":"10.1161\/JAHA.116.003976","article-title":"Oxidized Low-Density Lipoprotein (OxLDL)-Treated Dendritic Cells Promote Activation of T Cells in Human Atherosclerotic Plaque and Blood, Which Is Repressed by Statins: MicroRNA let-7c Is Integral to the Effect","volume":"5","author":"Zhang","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1038\/82219","article-title":"Statins as a newly recognized type of immunomodulator","volume":"6","author":"Kwak","year":"2000","journal-title":"Nat. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1189\/jlb.0205064","article-title":"Differential effects of statins on relevant functions of human monocyte-derived dendritic cells","volume":"79","author":"Yilmaz","year":"2006","journal-title":"J. Leukoc. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"148798","DOI":"10.1155\/2014\/148798","article-title":"Atorvastatin Represses the Angiotensin 2-Induced Oxidative Stress and Inflammatory Response in Dendritic Cells via the PI3K\/Akt\/Nrf2 Pathway","volume":"2014","author":"Ma","year":"2014","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4744","DOI":"10.4049\/jimmunol.0804311","article-title":"Statins Impair CD1d-Mediated Antigen Presentation through the Inhibition of Prenylation","volume":"182","author":"Khan","year":"2009","journal-title":"J. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Chen, X., Zhang, Z., Qiao, G., Sun, Z., and Lu, W. (2024). Immune and inflammatory insights in atherosclerosis: Development of a risk prediction model through single-cell and bulk transcriptomic analyses. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1448662"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1093\/rheumatology\/keh663","article-title":"Aberrant production of soluble costimulatory molecules CTLA-4, CD28, CD80 and CD86 in patients with systemic lupus erythematosus","volume":"44","author":"Wong","year":"2005","journal-title":"Rheumatology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jneuroim.2007.01.007","article-title":"Soluble costimulatory factors sCD28, sCD80, sCD86 and sCD152 in relation to other markers of immune activation in patients with myasthenia gravis","volume":"185","author":"Kakoulidou","year":"2007","journal-title":"J. Neuroimmunol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Zen, R.C., Dominguez, W.V., Braga, I., Reis, L.M., Jorge, L.B., Yu, L., Woronik, V., and Dias, C.B. (2023). Urinary CD80 and Serum suPAR as Biomarkers of Glomerular Disease among Adults in Brazil. Diagnostics, 13.","DOI":"10.3390\/diagnostics13020203"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Chang, C.S., Chang, J.H., Hsu, N.C., Lin, H.Y., and Chung, C.Y. (2007). Expression of CD80 and CD86 costimulatory molecules are potential markers for better survival in nasopharyngeal carcinoma. BMC Cancer, 7.","DOI":"10.1186\/1471-2407-7-88"},{"key":"ref_89","unstructured":"Schonbeck, U., Ridker, P., and Libby, P. (2007). Soluble CD40L (CD154) as a Prognostic Marker of Atherosclerotic Diseases. (US20030152566A1), U.S. Patent."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Ozde, S., Mehdizade, C., Ozel, M.A., Ozde, C., Kayapinar, O., and Erguven, M. (2025). Evaluation of Plasma Soluble CD40 Ligand Levels in Children with Familial Mediterranean Fever and Its Relationship with Carotid Intima-Media Thickness. Diagnostics, 15.","DOI":"10.3390\/diagnostics15091077"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1161\/01.CIR.0000020548.60110.76","article-title":"Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography","volume":"105","author":"Rudd","year":"2002","journal-title":"Circulation"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/j.jacc.2011.12.037","article-title":"Coronary arterial 18F-sodium fluoride uptake: A novel marker of plaque biology","volume":"59","author":"Dweck","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jcmg.2013.12.003","article-title":"PET\/CT imaging of integrin alphavbeta3 expression in human carotid atherosclerosis","volume":"7","author":"Beer","year":"2014","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s11307-016-0987-0","article-title":"CD80 Is Upregulated in a Mouse Model with Shear Stress-Induced Atherosclerosis and Allows for Evaluating CD80-Targeting PET Tracers","volume":"19","author":"Meletta","year":"2017","journal-title":"Mol. Imaging Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1161\/CIRCULATIONAHA.105.590018","article-title":"Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress","volume":"113","author":"Cheng","year":"2006","journal-title":"Circulation"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1007\/s11307-020-01543-3","article-title":"In Vivo Imaging of Local Inflammation: Monitoring LPS-Induced CD80\/CD86 Upregulation by PET","volume":"23","author":"Taddio","year":"2021","journal-title":"Mol. Imaging Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"8090","DOI":"10.1021\/acs.jmedchem.9b00858","article-title":"Synthesis and Structure-Affinity Relationship of Small Molecules for Imaging Human CD80 by Positron Emission Tomography","volume":"62","author":"Taddio","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_98","first-page":"144","article-title":"Immune checkpoint inhibitor-induced myocarditis: A comprehensive review with clinical case insights","volume":"6","author":"Guerra","year":"2025","journal-title":"Arch. Peru. Cardiol. Circ. Cardiovasc."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Huang, S., Kang, Y., Liu, T., Xiong, Y., Yang, Z., and Zhang, Q. (2025). The role of immune checkpoints PD-1 and CTLA-4 in cardiovascular complications leading to heart failure. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1561968"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.3899\/jrheum.170926","article-title":"Cardiovascular (CV) Risk after Initiation of Abatacept versus TNF Inhibitors in Rheumatoid Arthritis Patients with and without Baseline CV Disease","volume":"45","author":"Jin","year":"2018","journal-title":"J. Rheumatol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e007393","DOI":"10.1161\/JAHA.117.007393","article-title":"Comparative Cardiovascular Risk of Abatacept and Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis with and Without Diabetes Mellitus","volume":"7","author":"Kang","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_102","first-page":"1739","article-title":"Biologic Agents Reduce Cardiovascular Events in Rheumatoid Arthritis Not Responsive to Tumour Necrosis Factor Inhibitors: A National Cohort Study","volume":"36","author":"Hsieh","year":"2020","journal-title":"Can. J. Cardiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13075-024-03323-8","article-title":"Long-term effects of abatacept on atherosclerosis and arthritis in older vs. younger patients with rheumatoid arthritis: 3-year results of a prospective, multicenter, observational study","volume":"26","author":"Yamada","year":"2024","journal-title":"Arthritis Res. Ther."},{"key":"ref_104","unstructured":"Cush, J. (RheumNow, 2018). Less Cardiovascular Risk with Abatacept in Rheumatoid Arthritis, RheumNow."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Provan, S.A., Berg, I.J., Hammer, H.B., Mathiessen, A., Kvien, T.K., and Semb, A.G. (2015). The Impact of Newer Biological Disease Modifying Anti-Rheumatic Drugs on Cardiovascular Risk Factors: A 12-Month Longitudinal Study in Rheumatoid Arthritis Patients Treated with Rituximab, Abatacept and Tocilizumab. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130709"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s41181-019-0078-z","article-title":"Tracers for non-invasive radionuclide imaging of immune checkpoint expression in cancer","volume":"4","author":"Wierstra","year":"2019","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Han, Y., Xu, H., Yao, X., Li, Z., Zhu, C., Li, X., Chen, B., and Sun, H. (2026). Molecular mechanisms and therapeutic progress in atherosclerosis: Bridging immune inflammation and precision medicine. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1737662"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8215\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:35:34Z","timestamp":1789479334000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":107,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27188215"],"URL":"https:\/\/doi.org\/10.3390\/ijms27188215","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}