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After AMI in mice and humans, the number of extracellular vesicles (EVs) increased acutely. In humans, EV number correlated closely with the extent of myocardial injury. We hypothesized that EVs mediate splenic monocyte mobilization and program transcription following AMI. Some plasma EVs bear endothelial cell (EC) integrins, and both proinflammatory stimulation of ECs and AMI significantly increased VCAM-1\u2013positive EV release. Injected EC-EVs localized to the spleen and interacted with, and mobilized, splenic monocytes in otherwise naive, healthy animals. Analysis of human plasma EV-associated miRNA showed 12 markedly enriched miRNAs after AMI; functional enrichment analyses identified 1,869 putative mRNA targets, which regulate relevant cellular functions (e.g., proliferation and cell movement). Furthermore, gene ontology termed positive chemotaxis as the most enriched pathway for the miRNA-mRNA targets. Among the identified EV miRNAs, EC-associated miRNA-126-3p and -5p were highly regulated after AMI. miRNA-126-3p and -5p regulate cell adhesion\u2013 and chemotaxis-associated genes, including the negative regulator of cell motility, plexin-B2. EC-EV exposure significantly downregulated plexin-B2 mRNA in monocytes and upregulated motility integrin ITGB2. These findings identify EVs as a possible novel signaling pathway by linking ischemic myocardium with monocyte mobilization and transcriptional activation following AMI.<\/jats:p>","DOI":"10.1172\/jci.insight.93344","type":"journal-article","created":{"date-parts":[[2017,9,6]],"date-time":"2017-09-06T17:27:40Z","timestamp":1504718860000},"source":"Crossref","is-referenced-by-count":109,"title":["Endothelium-derived extracellular vesicles promote splenic monocyte mobilization in myocardial infarction"],"prefix":"10.1172","volume":"2","author":[{"given":"Naveed","family":"Akbar","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet E.","family":"Digby","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Cahill","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijeet N.","family":"Tavare","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alastair L.","family":"Corbin","sequence":"additional","affiliation":[{"name":"Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushant","family":"Saluja","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9457-0570","authenticated-orcid":true,"given":"Sam","family":"Dawkins","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7893-2324","authenticated-orcid":true,"given":"Laurienne","family":"Edgar","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadiia","family":"Rawlings","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3819-3779","authenticated-orcid":true,"given":"Klemen","family":"Ziberna","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0971-9858","authenticated-orcid":true,"given":"Eileen","family":"McNeill","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Oxford Acute Myocardial Infarction (OxAMI) Study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Errin","family":"Johnson","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa A.","family":"Aljabali","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Radcliffe Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Dragovic","sequence":"additional","affiliation":[{"name":"Nuffield Department of Obstetrics and Gynaecology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mala","family":"Rohling","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6962-7894","authenticated-orcid":true,"given":"T. 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