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Aortic stenosis often coexists with CAD (ASCAD), representing an advanced disease form. This study investigates immune pathways in isolated CAD (iCAD) and ASCAD. For this purpose, peripheral blood from 72 individuals (healthy donors, iCAD, and ASCAD patients) was analysed via flow cytometry to assess immune populations. Circulating cytokine levels were measured, and machine learning models identified predictive immune biomarkers. Our data showed that both iCAD and ASCAD patients exhibited immune dysregulation, with reduced dendritic cells, basophils, NK cells, B cells, and T cells, alongside lower frequencies of DCs, lymphocytes, CD8+CD28+ T cells, and CD57+ T cells. Elevated IL-15 and fractalkine, but reduced IL-8 and MCP-1, suggest impaired monocyte and neutrophil mobilisation due to immune cell sequestration in vascular lesions. Distinct immune features emerged between iCAD and ASCAD. iCAD patients showed heightened immune activation, with increased inflammatory CD14+CD16+ monocytes, higher Treg frequencies, and greater CD4+ T cell differentiation into TEM and TEMRA phenotypes. In contrast, ASCAD patients exhibited pronounced immunosenescence, with higher neutrophil counts, lymphopenia, and increased NK and T cell cytotoxicity. Our predictive model distinguished iCAD from ASCAD with high accuracy, identifying CD4+ T cell memory subsets and CD57 expression as key discriminators. This study reveals iCAD as being driven by immune activation and ASCAD by immunosenescence and cytotoxicity. These insights advance CAD immunopathology understanding and support immune-based classification, particularly for ASCAD, where treatment remains limited to surgical intervention.<\/jats:p>","DOI":"10.3390\/ijms26115248","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T06:14:27Z","timestamp":1748585667000},"page":"5248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Divergent Immune Pathways in Coronary Artery Disease and Aortic Stenosis: The Role of Chronic Inflammation and Senescence"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9400-208X","authenticated-orcid":false,"given":"Jos\u00e9 Joaqu\u00edn","family":"Dom\u00ednguez-del-Castillo","sequence":"first","affiliation":[{"name":"Cardiovascular Pathology Group (GA09), Maimonides Biomedical Research Institute, University of Cordoba, Reina Sofia University Hospital, Avda Menedez Pidal s\/n, 14004 Cordoba, Spain"},{"name":"Department of Cell Biology, Physiology and Immunology, University of Cordoba, Avda Menedez Pidal s\/n, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4153-2236","authenticated-orcid":false,"given":"Pablo","family":"\u00c1lvarez-Heredia","sequence":"additional","affiliation":[{"name":"Immunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia University Hospital, Avda Menedez Pidal s\/n, 14004 Cordoba, Spain"},{"name":"Hospital Nostra Senyora de Meritxell, Avinguda Fiter i Rossell 13, AD700 Escaldes-Engordany, Andorra"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Reina-Alfonso","sequence":"additional","affiliation":[{"name":"Immunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia University Hospital, Avda Menedez Pidal s\/n, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0288-1055","authenticated-orcid":false,"given":"Maria-Isabel","family":"Vallejo-Berm\u00fadez","sequence":"additional","affiliation":[{"name":"Immunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia University Hospital, Avda Menedez Pidal s\/n, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosal\u00eda","family":"L\u00f3pez-Romero","sequence":"additional","affiliation":[{"name":"Cardiovascular Pathology Group (GA09), Maimonides Biomedical Research Institute, University of Cordoba, Reina Sofia University Hospital, Avda Menedez Pidal s\/n, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Antonio","family":"Moreno-Moreno","sequence":"additional","affiliation":[{"name":"Cardiovascular Pathology Group (GA09), Maimonides Biomedical Research Institute, University of Cordoba, Reina Sofia University Hospital, Avda Menedez Pidal s\/n, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Bilbao-Carrasco","sequence":"additional","affiliation":[{"name":"Cardiovascular Pathology Group (GA09), Maimonides Biomedical Research Institute, University of Cordoba, Reina Sofia University Hospital, Avda Menedez Pidal s\/n, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Moya-Gonzalez","sequence":"additional","affiliation":[{"name":"Cardiovascular Pathology Group (GA09), Maimonides Biomedical Research Institute, University of Cordoba, Reina Sofia University Hospital, Avda Menedez Pidal s\/n, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Mu\u00f1oz-Calero","sequence":"additional","affiliation":[{"name":"Cardiovascular Pathology Group (GA09), Maimonides Biomedical Research Institute, University of Cordoba, Reina Sofia University Hospital, Avda Menedez Pidal s\/n, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2926-6377","authenticated-orcid":false,"given":"Raquel","family":"Tarazona","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Physiology, University of Extremadura, 10003 C\u00e1ceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8985-0295","authenticated-orcid":false,"given":"Rafael","family":"Solana","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology, University of Cordoba, Avda Menedez Pidal s\/n, 14004 Cordoba, Spain"},{"name":"Immunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia University Hospital, Avda Menedez Pidal s\/n, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Batista-Duharte","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology, University of Cordoba, Avda Menedez Pidal s\/n, 14004 Cordoba, Spain"},{"name":"Immunology and Allergy Group (GC01), Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Reina Sofia University Hospital, Avda Menedez Pidal s\/n, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3843-8609","authenticated-orcid":false,"given":"Ignacio","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Cardiovascular Pathology Group (GA09), Maimonides Biomedical Research 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therapeutics","volume":"234","author":"Malakar","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"169","DOI":"10.2991\/jegh.k.201217.001","article-title":"Epidemiology and the Magnitude of Coronary Artery Disease and Acute Coronary Syndrome: A Narrative Review","volume":"11","author":"Ralapanawa","year":"2021","journal-title":"J. Epidemiol. Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/s41569-021-00668-4","article-title":"Therapeutic strategies targeting inflammation and immunity in atherosclerosis: How to proceed?","volume":"19","author":"Engelen","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s00395-022-00935-6","article-title":"Innate immune cells in the pathophysiology of calcific aortic valve disease: Lessons to be learned from atherosclerotic cardiovascular disease?","volume":"117","author":"Broeders","year":"2022","journal-title":"Basic. Res. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ghamar Talepoor, A., and Doroudchi, M. (2022). Immunosenescence in atherosclerosis: A role for chronic viral infections. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.945016"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6572","DOI":"10.4049\/jimmunol.162.11.6572","article-title":"Modulation of CD28 expression: Distinct regulatory pathways during activation and replicative senescence","volume":"162","author":"Vallejo","year":"1999","journal-title":"J. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1093\/gerona\/glab140","article-title":"Impact of Cytomegalovirus and Age on T-Cell Subsets Defined by CD161, CD300a, and\/or CD57 Expression in Healthy Andalusians","volume":"76","author":"Formentini","year":"2021","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1093\/infdis\/jiad119","article-title":"Accelerated T-Cell Immunosenescence in Cytomegalovirus-Seropositive Individuals After Severe Acute Respiratory Syndrome Coronavirus 2 Infection","volume":"228","author":"Hassouneh","year":"2023","journal-title":"J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Broadley, I., Pera, A., Morrow, G., Davies, K.A., and Kern, F. (2017). Expansions of Cytotoxic CD4(+)CD28(-) T Cells Drive Excess Cardiovascular Mortality in Rheumatoid Arthritis and Other Chronic Inflammatory Conditions and Are Triggered by CMV Infection. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00195"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.4049\/jimmunol.165.2.1138","article-title":"Killer cell activating receptors function as costimulatory molecules on CD4+CD28null T cells clonally expanded in rheumatoid arthritis","volume":"165","author":"Namekawa","year":"2000","journal-title":"J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cellimm.2013.01.007","article-title":"Characterization of CD4+CD28null T cells in patients with coronary artery disease and individuals with risk factors for atherosclerosis","volume":"281","author":"Teo","year":"2013","journal-title":"Cell. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/cvr\/cvn248","article-title":"CD4+ CD28 null T cells in coronary artery disease: When helpers become killers","volume":"81","author":"Dumitriu","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.atherosclerosis.2012.07.033","article-title":"Persistent accumulation of interferon-\u03b3-producing CD8+CD56+ T cells in blood from patients with coronary artery disease","volume":"224","author":"Backteman","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ijcard.2015.04.063","article-title":"Disease complexity in acute coronary syndrome is related to the patient\u2019s immunological status","volume":"189","author":"Avanzas","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1093\/eurheartj\/ehu247","article-title":"Aortic stenosis and coronary artery disease: What do we know? What don\u2019t we know? A comprehensive review of the literature with proposed treatment algorithms","volume":"35","author":"Paradis","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_16","unstructured":"Pujari, S.H., and Agasthi, P. (2025). Aortic Stenosis. StatPearls, StatPearls Publishing."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Di Gioia, G., Bartunek, J., Tesorio, T., Vukcevic, V., Aleksandric, S., Dobric, M., Franco, D., Barbato, E., and Banovic, M. (2021). Pathophysiology, Diagnosis, and Treatment of Patients with Concomitant Severe Aortic Stenosis and Coronary Artery Disease: A Closer Look to the Unresolved Perplexity. J. Clin. Med., 10.","DOI":"10.3390\/jcm10081617"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"16006","DOI":"10.1038\/nrdp.2016.6","article-title":"Calcific aortic stenosis","volume":"2","author":"Lindman","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"08","DOI":"10.12703\/P7-08","article-title":"Pathophysiology of coronary artery disease leading to acute coronary syndromes","volume":"7","author":"Ambrose","year":"2015","journal-title":"F1000Prime Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e1462","DOI":"10.1002\/cti2.1462","article-title":"Mass cytometry analysis reveals altered immune profiles in patients with coronary artery disease","volume":"12","author":"Kott","year":"2023","journal-title":"Clin. Transl. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Iqneibi, S., Saigusa, R., Khan, A., Oliaeimotlagh, M., Armstrong Suthahar, S.S., Kumar, S., Alimadadi, A., Durant, C.P., Ghosheh, Y., and McNamara, C.A. (2023). Single cell transcriptomics reveals recent CD8T cell receptor signaling in patients with coronary artery disease. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1239148"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1093\/cvr\/cvaa202","article-title":"Interleukin-7 and interleukin-15 drive CD4+CD28null T lymphocyte expansion and function in patients with acute coronary syndrome","volume":"117","author":"Bullenkamp","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1172\/JCI12877","article-title":"The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium","volume":"108","author":"Huo","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/clc.4960250403","article-title":"Monocyte chemoattractant protein-1 and coronary artery disease","volume":"25","author":"Ikeda","year":"2002","journal-title":"Clin. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1046\/j.1365-2362.2002.01053.x","article-title":"Selectin-P and interleukin-8 plasma levels in coronary heart disease patients","volume":"32","author":"Romuk","year":"2002","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1161\/01.ATV.0000134294.54422.2e","article-title":"IL-8 plasma concentrations and the risk of future coronary artery disease in apparently healthy men and women: The EPIC-Norfolk prospective population study","volume":"24","author":"Boekholdt","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.imlet.2017.08.010","article-title":"The potential and promise of IL-15 in immuno-oncogenic therapies","volume":"190","author":"Robinson","year":"2017","journal-title":"Immunol. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Loh, S.X., Ekinci, Y., Spray, L., Jeyalan, V., Olin, T., Richardson, G., Austin, D., Alkhalil, M., and Spyridopoulos, I. (2023). Fractalkine Signalling (CX(3)CL1\/CX(3)CR1 Axis) as an Emerging Target in Coronary Artery Disease. J. Clin. Med., 12.","DOI":"10.3390\/jcm12144821"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"132741","DOI":"10.1016\/j.ijcard.2024.132741","article-title":"Atherosclerosis, calcific aortic valve disease and mitral annular calcification: Same or different?","volume":"420","author":"Hafiane","year":"2025","journal-title":"Int. J. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1340","DOI":"10.1002\/iid3.1340","article-title":"Prognosis impact of multiple novel lymphocyte-based inflammatory indices in patients with initially diagnosed coronary artery disease","volume":"12","author":"Gao","year":"2024","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.4049\/jimmunol.1003521","article-title":"Circulating activated and effector memory T cells are associated with calcification and clonal expansions in bicuspid and tricuspid valves of calcific aortic stenosis","volume":"187","author":"Winchester","year":"2011","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"\u00c1lvarez-Heredia, P., Dom\u00ednguez-del-Castillo, J.J., Reina-Alfonso, I., Guti\u00e9rrez-Gonz\u00e1lez, C., Hassouneh, F., Batista-Duharte, A., Trujillo-Aguilera, A., L\u00f3pez-Romero, R., Mu\u00f1oz, I., and Solana, R. (2023). A Straightforward Cytometry-Based Protocol for the Comprehensive Analysis of the Inflammatory Valve Infiltrate in Aortic Stenosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032194"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1046\/j.1365-2796.2003.01217.x","article-title":"Expansion of peripheral CD8+ T cells in patients with coronary artery disease: Relation to cytomegalovirus infection","volume":"254","author":"Jonasson","year":"2003","journal-title":"J. Intern. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/imm.13824","article-title":"IL-10 indirectly modulates functional activity of CD4(+)CD28(null) T-lymphocytes through LFA-3 and HLA class II inhibition","volume":"173","author":"Rioseras","year":"2024","journal-title":"Immunology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4509","DOI":"10.7150\/thno.27428","article-title":"CD28(null) pro-atherogenic CD4 T-cells explain the link between CMV infection and an increased risk of cardiovascular death","volume":"8","author":"Pera","year":"2018","journal-title":"Theranostics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1161\/CIRCRESAHA.116.309982","article-title":"Cytomegalovirus as a Driver of Excess Cardiovascular Mortality in Rheumatoid Arthritis: A Red Herring or a Smoking Gun?","volume":"120","author":"Pera","year":"2017","journal-title":"Circ. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"413","DOI":"10.2133\/dmpk.19.413","article-title":"Immunosuppressive interactions among calcium channel antagonists and selected corticosteroids and macrolides using human whole blood lymphocytes","volume":"19","author":"Chow","year":"2004","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1152\/physrev.00031.2016","article-title":"Role of the Immune System in Hypertension","volume":"97","author":"Pons","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Felkle, D., Jarczynski, M., Kaleta, K., Zieba, K., and Nazimek, K. (2022). The immunomodulatory effects of antihypertensive therapy: A review. Biomed. 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