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Although it is widely posited that endothelial cell dysfunction contributes to the pathogenesis and\/or progression of AD\/ADRD, it is not clear how. A plausible hypothesis is that intercellular trafficking of extracellular vesicles (EVs) from senescent vascular endothelial cells promotes vascular endothelial cell dysfunction. To test this hypothesis, we compared the expression of proteins and miRNAs in EVs isolated from four sets of genetically identical early passage non\u2010senescent (EP) versus late passage senescent (SEN) primary human coronary artery endothelial cells (HCAECs) derived from four donors. Proteomics and miRNA libraries constructed from these EV isolates were evaluated using FunRich gene ontology analysis to compare functional enrichment between EP and SEN endothelial cell EVs (ECEVs). Replicative senescence was associated with altered EV abundance and contents independent of changes in EV size. Unique sets of miRNAs and proteins were differentially expressed in SEN\u2010ECEVs, including molecules related to cell adhesion, barrier integrity, receptor signalling, endothelial\u2010mesenchymal transition and cell senescence. miR\u2010181a\u20105p was the most upregulated miRNA in SEN\u2010ECEVs, increasing &gt;5\u2010fold. SEN\u2010ECEV proteomes supported involvement in several pro\u2010inflammatory pathways consistent with senescence and the senescence\u2010associated secretory phenotype (SASP). These data indicate that SEN\u2010ECEVs are enriched in bioactive molecules implicated in senescence\u2010associated vascular dysfunction, blood\u2013brain barrier impairment, and AD\/ADRD pathology. These observations suggest involvement of SEN\u2010ECEVs in the pathogenesis of vascular dysfunction associated with AD\/ADRD.<\/jats:p>","DOI":"10.1002\/jex2.70078","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T03:04:05Z","timestamp":1753931045000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Multiomics Profiling of Extracellular Vesicles Supports Their Involvement in Endothelial Senescence\u2010Associated Vascular Dysfunction"],"prefix":"10.1002","volume":"4","author":[{"given":"Ryan E.","family":"Hogans","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine University of California  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine, School of 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