{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:38:53Z","timestamp":1785411533887,"version":"3.56.0"},"reference-count":98,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["PNRR-POC-2023-12378186 CUP I73C24000330006"],"award-info":[{"award-number":["PNRR-POC-2023-12378186 CUP I73C24000330006"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"award":["PNRR-POC-2023-12378186 CUP I73C24000330006"],"award-info":[{"award-number":["PNRR-POC-2023-12378186 CUP I73C24000330006"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Coronary artery disease (CAD) is increasingly recognized as a thromboinflammatory disorder in which innate immune activation and coagulation are tightly coupled within the plaque microenvironment. Emerging single-cell and spatial technologies have refined this paradigm by demonstrating that these processes are not diffusely distributed but instead concentrated within discrete cellular niches. This narrative review critically evaluates mechanistic and translational studies integrating single-cell RNA sequencing, spatial transcriptomics, and ligand\u2013receptor modeling to characterize cell\u2013cell communication networks driving immunothrombosis in CAD. Converging evidence from single-cell and spatial studies indicates substantial heterogeneity among macrophages, neutrophils, and smooth muscle cells, with functionally distinct subpopulations contributing differentially to inflammation, matrix remodeling, and thrombogenicity. Spatial analyses further demonstrate that procoagulant and inflammatory programs converge in anatomically defined high-risk regions, particularly at the plaque shoulder and sites of endothelial dysfunction. However, whether these transcriptional states represent causal drivers or epiphenomena remains unresolved. Many insights are derived from murine models or dissociated tissues, raising concerns regarding translational relevance and loss of spatial context. Additionally, computational inference of intercellular communication remains indirect and requires functional validation. In conclusion, immunothrombosis in CAD should be interpreted as an emergent property of spatially organized cellular networks rather than a uniform inflammatory state. While these approaches identify candidate therapeutic nodes, their clinical translation and the central challenge is to distinguish causal regulatory nodes from transcriptional correlates generated by high-dimensional profiling.<\/jats:p>","DOI":"10.3390\/ijms27135900","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:50:37Z","timestamp":1782867037000},"page":"5900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunothrombotic Cell\u2013Cell Communication Networks in Coronary Atherosclerosis: Critical Insights from Single-Cell and Spatial Systems Biology"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3464-1645","authenticated-orcid":false,"given":"Beata","family":"Krasi\u0144ska","sequence":"first","affiliation":[{"name":"Department of Hypertensiology, Angiology, and Internal Medicine, Poznan University of Medical Sciences, 61-848 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0193-8094","authenticated-orcid":false,"given":"Antoni","family":"Staniewski","sequence":"additional","affiliation":[{"name":"Student Research Group of Cardiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliwia","family":"Kalus","sequence":"additional","affiliation":[{"name":"Student Research Group of Cardiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Ma\u0107kowiak","sequence":"additional","affiliation":[{"name":"Student Research Group of Cardiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0904-0793","authenticated-orcid":false,"given":"Zofia","family":"Szyma\u0144ska","sequence":"additional","affiliation":[{"name":"Student Research Group of Cardiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6210-3109","authenticated-orcid":false,"given":"Zofia","family":"Gramala","sequence":"additional","affiliation":[{"name":"Student Research Group of Cardiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9896-9293","authenticated-orcid":false,"given":"Katarzyna","family":"Zalewska","sequence":"additional","affiliation":[{"name":"Student Research Group of Cardiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Karpi\u0144ski","sequence":"additional","affiliation":[{"name":"Student Research Group of Cardiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9530-6659","authenticated-orcid":false,"given":"Paulina","family":"Mertowska","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Faculty of Medical Sciences, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0141ucja","family":"Rolek","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Faculty of Medical Sciences, Medical University of Lublin, 20-093 Lublin, Poland"},{"name":"Student Research Group of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Koziarska","sequence":"additional","affiliation":[{"name":"Central University Hospital, Poznan University of Medical Sciences, 60-352 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6563-0877","authenticated-orcid":false,"given":"Krzysztof J.","family":"Filipiak","sequence":"additional","affiliation":[{"name":"The Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansur","family":"Rahnama","sequence":"additional","affiliation":[{"name":"Department of Dental Surgery, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5478-3245","authenticated-orcid":false,"given":"Mariusz","family":"Kowalewski","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Center of Postgraduate Medical Education, Central Clinical Hospital of the Ministry of Interior, 02-507 Warszawa, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calogera","family":"Pisano","sequence":"additional","affiliation":[{"name":"Department of Research, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), 90127 Palermo, Italy"},{"name":"Department of Precision Medicine in Medical Surgical and Critical Area (Me.Pre.C.C.), University of Palermo, 90134 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe Maria","family":"Raffa","sequence":"additional","affiliation":[{"name":"Department of Research, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), 90127 Palermo, Italy"},{"name":"Department of Precision Medicine in Medical Surgical and Critical Area (Me.Pre.C.C.), University of Palermo, 90134 Palermo, 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atherosclerosis","volume":"124","author":"Wolf","year":"2019","journal-title":"Circ. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/pin.12921","article-title":"Pathophysiology of atherothrombosis: Mechanisms of thrombus formation on disrupted atherosclerotic plaques","volume":"70","author":"Asada","year":"2020","journal-title":"Pathol. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/s41569-021-00552-1","article-title":"Interplay between inflammation and thrombosis in cardiovascular pathology","volume":"18","author":"Stark","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1200341","DOI":"10.3389\/fcvm.2023.1200341","article-title":"Molecular and cellular mechanisms of inflammation in atherosclerosis","volume":"10","author":"Ferdoschi","year":"2023","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","unstructured":"Starikova, E.A., Mammedova, J.T., Rubinstein, A.A., Sokolov, A.V., and Kudryavtsev, I.V. (2025). Activation of the coagulation cascade as a universal danger sign. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47020108"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri3345","article-title":"Thrombosis as an intravascular effector of innate immunity","volume":"13","author":"Engelmann","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1177\/17534259231189195","article-title":"Role of neutrophils in different stages of atherosclerosis","volume":"29","author":"Zhang","year":"2023","journal-title":"Innate Immun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1093\/cvr\/cvaf105","article-title":"Platelet-leukocyte aggregates in cardiovascular disease: Prognostic significance and therapeutic potential","volume":"121","author":"Han","year":"2025","journal-title":"Cardiovasc. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"824112","DOI":"10.3389\/fcvm.2021.824112","article-title":"Neutrophil-platelet interactions as novel treatment targets in cardiovascular disease","volume":"8","author":"Kaiser","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"107499","DOI":"10.1016\/j.vph.2025.107499","article-title":"Single-cell RNA sequencing (scRNA-seq) and its insights into cellular heterogeneity in atherosclerosis","volume":"159","author":"Yu","year":"2025","journal-title":"Vasc. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e19392","DOI":"10.1016\/j.heliyon.2023.e19392","article-title":"Immune landscape and regulatory mechanisms in human atherosclerotic coronary plaques: Evidence from single-cell and bulk transcriptomics","volume":"9","author":"Liang","year":"2023","journal-title":"Heliyon"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.1038\/s44321-025-00280-w","article-title":"Spatial transcriptomics elucidates localized immune responses in atherosclerotic coronary artery","volume":"17","author":"Campos","year":"2025","journal-title":"EMBO Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1016\/j.jacc.2023.04.008","article-title":"Spatial transcriptional mapping reveals site-specific pathways underlying human atherosclerotic plaque rupture","volume":"81","author":"Sun","year":"2023","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1161\/HYPERTENSIONAHA.121.17957","article-title":"Role of extracellular vesicles in the pathogenesis of vascular damage","volume":"79","author":"Buffolo","year":"2022","journal-title":"Hypertension"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/imr.13127","article-title":"Extracellular vesicles in atherothrombosis: From biomarkers and precision medicine to therapeutic targets","volume":"312","author":"Badimon","year":"2022","journal-title":"Immunol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Suades, R., Greco, M.F., Padr\u00f3, T., and Badimon, L. (2022). Extracellular vesicles as drivers of immunoinflammation in atherothrombosis. Cells, 11.","DOI":"10.3390\/cells11111845"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Muttiah, B., Ng, S.L., Lokanathan, Y., Ng, M.H., and Law, J.X. (2024). Beyond blood clotting: The many roles of platelet-derived extracellular vesicles. Biomedicines, 12.","DOI":"10.3390\/biomedicines12081850"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"813885","DOI":"10.3389\/fcell.2022.813885","article-title":"Role of extracellular vesicles as potential diagnostic and\/or therapeutic biomarkers in chronic cardiovascular diseases","volume":"10","author":"Roncal","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1016\/j.cell.2021.01.049","article-title":"Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis","volume":"184","author":"Heyde","year":"2021","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"a006251","DOI":"10.1101\/mcs.a006251","article-title":"Defining clonal hematopoiesis of indeterminate potential: Evolutionary dynamics and detection under aging and inflammation","volume":"9","author":"Goldman","year":"2023","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1161\/ATVBAHA.122.318928","article-title":"Clonal hematopoiesis of indeterminate potential is associated with coronary microvascular dysfunction in early nonobstructive coronary artery disease","volume":"43","author":"Akhiyat","year":"2023","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/s41569-025-01148-9","article-title":"Clonal haematopoiesis in cardiovascular disease: Prognostic role and novel therapeutic target","volume":"22","author":"Schuermans","year":"2025","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Medina-Leyte, D.J., Zepeda-Garc\u00eda, O., Dom\u00ednguez-P\u00e9rez, M., Gonz\u00e1lez-Garrido, A., Villarreal-Molina, T., and Jacobo-Albavera, L. (2021). Endothelial dysfunction, inflammation and coronary artery disease: Potential biomarkers and promising therapeutical approaches. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083850"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Olejarz, W., \u0141acheta, D., and Kubiak-Tomaszewska, G. (2020). Matrix metalloproteinases as biomarkers of atherosclerotic plaque instability. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113946"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Szyma\u0144ska, Z., Staniewski, A., Karpi\u0144ski, M., Zalewska, K., Kalus, O., Gramala, Z., Ma\u0107kowiak, J., Mertowski, S., Filipiak, K.J., and Rahnama-Hezavah, M. (2025). The role of neutrophil extracellular networks in cardiovascular pathology. Cells, 14.","DOI":"10.3390\/cells14191562"},{"key":"ref_28","first-page":"1205","article-title":"Neutrophil extracellular traps (NETs) in cardiovascular diseases: From molecular mechanisms to therapeutic interventions","volume":"81","author":"Natorska","year":"2023","journal-title":"Kardiol. Pol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"113380","DOI":"10.1016\/j.celrep.2023.113380","article-title":"Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis","volume":"42","author":"Mosquera","year":"2023","journal-title":"Cell Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1038\/s41591-019-0590-4","article-title":"Single-cell immune landscape of human atherosclerotic plaques","volume":"25","author":"Fernandez","year":"2019","journal-title":"Nat. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"599415","DOI":"10.3389\/fimmu.2020.599415","article-title":"Role of vascular smooth muscle cell plasticity and interactions in vessel wall inflammation","volume":"11","author":"Sorokin","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1161\/CIRCULATIONAHA.120.048378","article-title":"Single-cell genomics reveals a novel cell state during smooth muscle cell phenotypic switching and potential therapeutic targets for atherosclerosis in mouse and human","volume":"142","author":"Pan","year":"2020","journal-title":"Circulation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e2350464","DOI":"10.1002\/eji.202350464","article-title":"Macrophage heterogeneity in atherosclerosis: A matter of context","volume":"54","author":"Wieland","year":"2024","journal-title":"Eur. J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.ajpath.2024.01.004","article-title":"Advances in understanding cardiovascular disease pathogenesis through next-generation technologies","volume":"194","author":"Scott","year":"2024","journal-title":"Am. J. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.cmet.2016.11.001","article-title":"Applications and Limitations of Mouse Models for Understanding Human Atherosclerosis","volume":"25","author":"Zhao","year":"2017","journal-title":"Cell Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1093\/eurheartj\/ehac686","article-title":"Translational opportunities of single-cell biology in atherosclerosis","volume":"44","author":"Evans","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/nmeth.4437","article-title":"Single-cell sequencing reveals dissociation-induced gene expression in tissue subpopulations","volume":"14","author":"Sage","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e1900221","DOI":"10.1002\/bies.201900221","article-title":"Spatially Resolved Transcriptomes-Next Generation Tools for Tissue Exploration","volume":"42","author":"Asp","year":"2020","journal-title":"Bioessays"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s12105-025-01876-x","article-title":"Spatial transcriptomics and artificial intelligence: A scoping review of emerging applications in head and neck pathology","volume":"20","author":"Yousef","year":"2026","journal-title":"Head Neck Pathol."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/s44161-023-00354-3","article-title":"Trem2 promotes foamy macrophage lipid uptake and survival in atherosclerosis","volume":"2","author":"Patterson","year":"2023","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s44161-024-00429-9","article-title":"TREM2 protects from atherosclerosis by limiting necrotic core formation","volume":"3","author":"Piollet","year":"2024","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s12915-023-01540-2","article-title":"Bulk and single-cell characterisation of the immune heterogeneity of atherosclerosis identifies novel targets for immunotherapy","volume":"21","author":"Xiong","year":"2023","journal-title":"BMC Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1161\/ATVBAHA.119.312434","article-title":"Smooth Muscle Cells Contribute the Majority of Foam Cells in ApoE (Apolipoprotein E)-Deficient Mouse Atherosclerosis","volume":"39","author":"Wang","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1161\/CIRCRESAHA.115.306361","article-title":"Vascular Smooth Muscle Cells in Atherosclerosis","volume":"118","author":"Bennett","year":"2016","journal-title":"Circ. Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Shafqat, A., Khan, J.A., Alkachem, A.Y., Sabur, H., Alkattan, K., Yaqinuddin, A., and Sing, G.K. (2023). How neutrophils shape the immune response: Reassessing their multifaceted role in health and disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417583"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/s44161-025-00714-1","article-title":"Coronary artery disease-associated variants regulate vascular smooth muscle cell gene expression","volume":"4","author":"Barbera","year":"2025","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/cvr\/cvs098","article-title":"Vascular smooth muscle cell phenotypic plasticity: Focus on chromatin remodelling","volume":"95","author":"Spin","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Poznyak, A.V., Nikiforov, N.G., Starodubova, A.V., Popkova, T.V., and Orekhov, A.N. (2021). Macrophages and foam cells: Brief overview of their role, linkage, and targeting potential in atherosclerosis. Biomedicines, 9.","DOI":"10.3390\/biomedicines9091221"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3741","DOI":"10.1111\/bph.14779","article-title":"The role of smooth muscle cells in plaque stability: Therapeutic targeting potential","volume":"176","author":"Harman","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1686947","DOI":"10.3389\/fcell.2025.1686947","article-title":"The pathophysiological mechanisms of immunosenescence in coronary artery disease","volume":"13","author":"Bie","year":"2025","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1038\/s41591-019-0512-5","article-title":"Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis","volume":"25","author":"Wirka","year":"2019","journal-title":"Nat. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1161\/CIRCRESAHA.120.316770","article-title":"Microanatomy of the Human Atherosclerotic Plaque by Single-Cell Transcriptomics","volume":"127","author":"Depuydt","year":"2020","journal-title":"Circ. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/s41421-021-00328-4","article-title":"Smooth muscle-derived macrophage-like cells contribute to multiple cell lineages in the atherosclerotic plaque","volume":"7","author":"Li","year":"2021","journal-title":"Cell Discov."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1161\/CIRCULATIONAHA.120.046672","article-title":"Stem Cell Pluripotency Genes Klf4 and Oct4 Regulate Complex SMC Phenotypic Changes Critical in Late-Stage Atherosclerotic Lesion Pathogenesis","volume":"142","author":"Alencar","year":"2020","journal-title":"Circulation"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Bu, L.L., Yuan, H.H., Xie, L.L., Guo, M.H., Liao, D.F., and Zheng, X.L. (2023). New dawn for atherosclerosis: Vascular endothelial cell senescence and death. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015160"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1055\/a-2561-2362","article-title":"High-resolution spatial profiling unveils cellular heterogeneity in murine atherosclerosis","volume":"125","author":"Wrobel","year":"2025","journal-title":"Thromb. Haemost."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s12964-023-01153-w","article-title":"Cellular crosstalk in atherosclerotic plaque microenvironment","volume":"21","author":"Mahdinia","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Petroni, D., Fabbri, C., Babboni, S., Menichetti, L., Basta, G., and Del Turco, S. (2023). Extracellular vesicles and intercellular communication: Challenges for in vivo molecular imaging and tracking. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15061639"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/978-981-99-1443-2_17","article-title":"Platelet-derived extracellular vesicles in arterial thrombosis","volume":"1418","author":"Harper","year":"2023","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1080\/09537104.2019.1639655","article-title":"Increased microvesicle-associated thrombin generation in patients with immune thrombocytopenia after initiation of thrombopoietin receptor agonists","volume":"31","author":"Garabet","year":"2020","journal-title":"Platelets"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"H2147","DOI":"10.1152\/ajpheart.00869.2020","article-title":"Microvesicles in plasma reflect coronary flow reserve in patients with cardiovascular disease","volume":"320","author":"James","year":"2021","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"733985","DOI":"10.3389\/fcvm.2021.733985","article-title":"Mechanisms of action of miRNAs and lncRNAs in extracellular vesicle in atherosclerosis","volume":"8","author":"Xu","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1080\/09537104.2022.2027903","article-title":"Does hsa-miR-223-3p from platelet-derived extracellular vesicles regulate tissue factor expression in monocytic cells?","volume":"33","author":"Collier","year":"2022","journal-title":"Platelets"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1080\/09537104.2017.1332366","article-title":"Comparison of the release of microRNAs and extracellular vesicles from platelets in response to different agonists","volume":"29","author":"Ambrose","year":"2018","journal-title":"Platelets"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.pathol.2021.05.099","article-title":"Erythrocyte interaction with neutrophil extracellular traps in coronary artery thrombosis following myocardial infarction","volume":"54","author":"Chilingaryan","year":"2022","journal-title":"Pathology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1055\/s-0041-1728763","article-title":"Linking neutrophil extracellular traps and platelet activation: A composite biomarker score for predicting outcomes after acute myocardial infarction","volume":"121","author":"Hally","year":"2021","journal-title":"Thromb. Haemost."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"102671","DOI":"10.1016\/j.ebiom.2020.102671","article-title":"Interactions between neutrophil extracellular traps and activated platelets enhance procoagulant activity in acute stroke patients with ICA occlusion","volume":"53","author":"Zhou","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1186\/s12967-025-06522-2","article-title":"Diagnostic and prognostic roles of endothelial- and platelet-derived extracellular vesicles in cardiovascular diseases","volume":"23","author":"Saeed","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"151311","DOI":"10.1016\/j.ejcb.2023.151311","article-title":"OxLDL sensitizes platelets for increased formation of extracellular vesicles capable of finetuning macrophage gene expression","volume":"102","author":"Maaninka","year":"2023","journal-title":"Eur. J. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"102847","DOI":"10.1016\/j.isci.2021.102847","article-title":"High glucose macrophage exosomes enhance atherosclerosis by driving cellular proliferation and hematopoiesis","volume":"24","author":"Bouchareychas","year":"2021","journal-title":"iScience"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.jconrel.2020.11.064","article-title":"Platelet-derived extracellular vesicles to target plaque inflammation for effective anti-atherosclerotic therapy","volume":"329","author":"Ma","year":"2021","journal-title":"J. Control Release"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Olejarz, W., Sadowski, K., and Radoszkiewicz, K. (2023). Extracellular vesicles in atherosclerosis: State of the art. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010388"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Russo, M., Gurgoglione, F.L., Russo, A., Rinaldi, R., Torlai Triglia, L., Foschi, M., Vigna, C., Vergallo, R., Montone, R.A., and Benedetto, U. (2025). Coronary artery disease and atherosclerosis in other vascular districts: Epidemiology, risk factors and atherosclerotic plaque features. Life, 15.","DOI":"10.3390\/life15081226"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/MOH.0000000000000688","article-title":"Clonal hematopoiesis driven by DNMT3A and TET2 mutations: Role in monocyte and macrophage biology and atherosclerotic cardiovascular disease","volume":"29","author":"Cobo","year":"2022","journal-title":"Curr. Opin. Hematol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1182\/bloodadvances.2024014430","article-title":"CHIP away at the marrow-clot connection: Inflammation, clonal hematopoiesis, and thromboembolic disease","volume":"9","author":"Todorovski","year":"2025","journal-title":"Blood Adv."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4678","DOI":"10.1038\/s41467-025-59333-w","article-title":"Epigenome-wide DNA methylation association study of CHIP provides insight into perturbed gene regulation","volume":"16","author":"Kirmani","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Anastasiou, I.A., Kounatidis, D., Vallianou, N.G., Rebelos, E., Karampela, I., and Dalamaga, M. (2025). Clonal hematopoiesis of indeterminate potential and cardiometabolic disease: Challenges, controversies and future perspectives. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27010233"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"117181","DOI":"10.1016\/j.atherosclerosis.2023.06.972","article-title":"Anti-inflammatory therapies were associated with reduced risk of myocardial infarction in patients with established cardiovascular disease or high cardiovascular risks: A systematic review and meta-analysis of randomized controlled trials","volume":"379","author":"Li","year":"2023","journal-title":"Atherosclerosis"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1161\/CIRCULATIONAHA.125.075769","article-title":"Incorporating management of clonal hematopoiesis of indeterminate potential into cardiovascular practice","volume":"152","author":"Oren","year":"2025","journal-title":"Circulation"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41392-022-00955-7","article-title":"Inflammation and atherosclerosis: Signaling pathways and therapeutic intervention","volume":"7","author":"Kong","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1002\/ptr.8203","article-title":"Modulation of atherosclerosis-related signaling pathways by Chinese herbal extracts: Recent evidence and perspectives","volume":"38","author":"Liu","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.3390\/cells12192359","article-title":"Innate immune pathways in atherosclerosis-from signaling to long-term epigenetic reprogramming","volume":"12","author":"Aronova","year":"2023","journal-title":"Cells"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00011-025-02058-9","article-title":"Clinical outcomes of anti-inflammatory therapies inhibiting the NLRP3\/IL-1\u03b2\/IL-6\/CRP pathway in coronary artery disease patients: A systemic review and meta-analysis of 37,056 individuals from 32 randomized trials","volume":"74","author":"Pan","year":"2025","journal-title":"Inflamm. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s11883-025-01387-8","article-title":"Role of interleukin-6 in atherothrombosis and myocardial infarction","volume":"28","author":"Huse","year":"2026","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Liu, H., Zhang, Y., Zhao, Y., Li, Y., Zhang, X., Bao, L., Yan, R., Yang, Y., Zhou, H., and Zhang, J. (2025). Research progress and clinical translation potential of coronary atherosclerosis diagnostic markers from a genomic perspective. Genes, 16.","DOI":"10.3390\/genes16010098"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"100015","DOI":"10.1016\/j.bvth.2024.100015","article-title":"Targeting the P-selectin\/PSGL-1 pathway: Discovery of disease-modifying therapeutics for disorders of thromboinflammation","volume":"1","author":"Escopy","year":"2024","journal-title":"Blood Vessel. Thromb. Hemost."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1186\/s12951-025-03384-0","article-title":"Targeted drug delivery systems for atherosclerosis","volume":"23","author":"Tu","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"21481","DOI":"10.1038\/s41598-023-48803-0","article-title":"In-silico study of drug delivery to atherosclerosis in the human carotid artery using metal-organic frameworks based on adhesion of nanocarriers","volume":"13","author":"Shamloo","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"101453","DOI":"10.1016\/j.nantod.2022.101453","article-title":"Harnessing nanotechnology for cardiovascular disease applications\u2014A comprehensive review based on bibliometric analysis","volume":"44","author":"Zheng","year":"2022","journal-title":"Nano Today"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"102238","DOI":"10.1016\/j.mtbio.2025.102238","article-title":"Advancements in nanomedicine for modulating ischemic cardiomyopathy therapy","volume":"34","author":"Ren","year":"2025","journal-title":"Mater. Today Bio."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e70277","DOI":"10.1002\/ctm2.70277","article-title":"Spatial omics strategies for investigating human carotid atherosclerotic disease","volume":"15","author":"Wan","year":"2025","journal-title":"Clin. Transl. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e264","DOI":"10.1161\/ATVBAHA.123.320330","article-title":"Spatial transcriptomic approach to understanding coronary atherosclerotic plaque stability","volume":"44","author":"Gastanadui","year":"2024","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1161\/CIRCRESAHA.117.312513","article-title":"Atlas of the Immune Cell Repertoire in Mouse Atherosclerosis Defined by Single-Cell RNA-Sequencing and Mass Cytometry","volume":"122","author":"Winkels","year":"2018","journal-title":"Circ. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e325795","DOI":"10.1161\/CIRCRESAHA.125.325795","article-title":"Advancing Cardiovascular Research with Single-Cell and Spatial Transcriptomics","volume":"138","author":"Li","year":"2026","journal-title":"Circ. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1510082","DOI":"10.3389\/fcvm.2025.1510082","article-title":"Single-cell and spatial analysis reveals the interaction between ITLN1+ foam cells and SPP1+ macrophages in atherosclerosis","volume":"12","author":"Li","year":"2025","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"9582430","DOI":"10.1155\/2016\/9582430","article-title":"Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis","volume":"2016","author":"Bobryshev","year":"2016","journal-title":"Biomed. Res. Int."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s43556-025-00337-9","article-title":"Neutrophil Extracellular Traps (NETs) in health and disease","volume":"6","author":"Shahzad","year":"2025","journal-title":"Mol. Biomed."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5900\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:31:25Z","timestamp":1783053085000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5900"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":98,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135900"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135900","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]}}}