{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T08:21:04Z","timestamp":1783066864859,"version":"3.54.6"},"posted":{"date-parts":[[2026,6,30]]},"group-title":"Immunology","reference-count":33,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Myocardial infarction (MI) triggers splenic immune cell trafficking to the heart. Vehicles that carry these signals and mediate this crosstalk are unknown.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Hypothesis<\/jats:title>\n                  <jats:p>We hypothesize that extracellular vesicles (EVs) released post-MI mediate splenic immune trafficking to the heart.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Mice were treated daily with an EV biogenesis inhibitor (GW4869) or vehicle. Splenic\/cardiac immune cells were assessed at 3d while survival, cardiac function, hypertrophy, and fibrosis were evaluated at 8w post-MI. Plasma EVs from 1d MI mice or from the hearts that underwent MI\/sham in a Langendorff system induced splenic immune trafficking to the heart within 3d and systolic dysfunction at 8w in na\u00efve mice.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    GW4869 i) inhibited splenic regression, ii) increased splenic retention of neutrophils, monocytes, dendritic cells (DCs), and CD4\u207a T-cells, iii) decreased cardiac gene expression of pro-inflammatory cytokines\/chemokines, and iv) decreased trafficking of immune cells to the hearts at 3d post-MI, and iii) improved systolic function and attenuated hypertrophy at 8w post-MI. MI EVs accumulated in the spleen and promoted egress of matured splenic immune cells upon administration to na\u00efve mice. Cardiac pro-inflammatory cytokines\/chemokines expression and CCR2\n                    <jats:sup>+<\/jats:sup>\n                    MHC-II\n                    <jats:sup>hi<\/jats:sup>\n                    infiltrating macrophages, CD11c\n                    <jats:sup>+<\/jats:sup>\n                    DCs, and CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    TNF\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    T-cell levels were also increased in na\u00efve mice at 3d post-injection. Importantly, transfer of MI EVs for 2 days induced systolic dysfunction, cellular hypertrophy, and fibrosis in na\u00efve mice at 8 w post-injection. DCs process MI EVs for T-cells activation.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>EVs mobilize splenic immune cells to the heart post-MI and their inhibition can subdue inflammatory tissue-damage to promote healing post-MI.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.23.734125","type":"posted-content","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T18:25:44Z","timestamp":1782843944000},"source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicles Mediate Activation and Trafficking of Splenic Immune Cells to the Heart Post-Myocardial Infarction"],"prefix":"10.64898","author":[{"given":"Kaneez","family":"Fatima","sequence":"first","affiliation":[{"name":"Heart and Vascular Institute"},{"name":"Departments of Medicine, Pennsylvania State University Milton S Hershey Medical Center, Hershey, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin","family":"Angelotti","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute"},{"name":"Departments of Medicine, Pennsylvania State University Milton S Hershey Medical Center, Hershey, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay","family":"Kumar","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute"},{"name":"Departments of Medicine, Pennsylvania State University Milton S Hershey Medical Center, Hershey, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishnu","family":"Chollangi","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute"},{"name":"Departments of Medicine, Pennsylvania State University Milton S Hershey Medical Center, Hershey, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1362-2429","authenticated-orcid":false,"given":"Wafa","family":"Aziz","sequence":"additional","affiliation":[{"name":"Heart and Vascular Institute"},{"name":"Departments of Medicine, Pennsylvania State University Milton S Hershey Medical Center, Hershey, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddarth","family":"Dasari","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily N.","family":"Bianchini","sequence":"additional","affiliation":[{"name":"Departments of Cell and Biological Systems, Pennsylvania State University Milton S Hershey Medical Center, Hershey, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Cell and Biological Systems, Pennsylvania State University Milton S Hershey Medical Center, Hershey, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9636-3161","authenticated-orcid":false,"given":"Suman","family":"Asalla","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6135-1897","authenticated-orcid":false,"given":"Harpreet","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, Dorothy M. 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