{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T01:01:52Z","timestamp":1793149312256,"version":"4.5.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2020,1,31]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Systemic inflammation compromises the reparative properties of endothelial progenitor cell (EPC) and their exosomes on myocardial repair, although the underlying mechanism of loss of function of exosomes from inflamed EPCs is still obscure.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To determine the mechanisms of IL-10 (interleukin-10) deficient-EPC\u2013derived exosome dysfunction in myocardial repair and to investigate if modification of specific exosome cargo can rescue reparative activity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Using IL-10 knockout mice mimicking systemic inflammation condition, we compared therapeutic effect and protein cargo of exosomes isolated from wild-type EPC and IL-10 knockout EPC. In a mouse model of myocardial infarction (MI), wild-type EPC-derived exosome treatment significantly improved left ventricle cardiac function, inhibited cell apoptosis, reduced MI scar size, and promoted post-MI neovascularization, whereas IL-10 knockout EPC-derived exosome treatment showed diminished and opposite effects. Mass spectrometry analysis revealed wild-type EPC-derived exosome and IL-10 knockout EPC-derived exosome contain different protein expression pattern. Among differentially expressed proteins, ILK (integrin-linked kinase) was highly enriched in both IL-10 knockout EPC-derived exosome as well as TNF\u03b1 (tumor necrosis factor-\u03b1)-treated mouse cardiac endothelial cell\u2013derived exosomes (TNF\u03b1 inflamed mouse cardiac endothelial cell\u2013derived exosome). ILK-enriched exosomes activated NF-\u03baB (nuclear factor \u03baB) pathway and NF-\u03baB\u2013dependent gene transcription in recipient endothelial cells and this effect was partly attenuated through ILK knockdown in exosomes. Intriguingly, ILK knockdown in IL-10 knockout EPC-derived exosome significantly rescued their reparative dysfunction in myocardial repair, improved left ventricle cardiac function, reduced MI scar size, and enhanced post-MI neovascularization in MI mouse model.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>IL-10 deficiency\/inflammation alters EPC-derived exosome function, content and therapeutic effect on myocardial repair by upregulating ILK enrichment in exosomes, and ILK-mediated activation of NF-\u03baB pathway in recipient cells, whereas ILK knockdown in exosomes attenuates NF-\u03baB activation and reduces inflammatory response. Our study provides new understanding of how inflammation may alter stem cell-exosome\u2013mediated cardiac repair and identifies ILK as a target kinase for improving progenitor cell exosome-based cardiac therapies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.119.315829","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T14:42:20Z","timestamp":1575902540000},"page":"315-329","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":148,"title":["Interleukin-10 Deficiency Alters Endothelial Progenitor Cell\u2013Derived Exosome Reparative Effect on Myocardial Repair via Integrin-Linked Kinase Enrichment"],"prefix":"10.1161","volume":"126","author":[{"given":"Yujia","family":"Yue","sequence":"first","affiliation":[{"name":"From the Center for Translational Medicine (Y.Y., C.W., C.B., G.H., M.T., R.R., M.C. V.N.S.G., Z.C., W.J.K., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlin","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine (Y.Y., C.W., C.B., G.H., M.T., R.R., M.C. V.N.S.G., Z.C., W.J.K., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Benedict","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine (Y.Y., C.W., C.B., G.H., M.T., R.R., M.C. V.N.S.G., Z.C., W.J.K., R.K.), Lewis Katz School of Medicine, Temple University, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Huang","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine (Y.Y., C.W., C.B., G.H., M.T., R.R., M.C. 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