{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T17:00:33Z","timestamp":1792342833229,"version":"4.4.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":1588,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Previous studies have demonstrated that transient myocardial ischemia leads to release of cellular nucleic acids such as RNA. Extracellular RNA reportedly plays a pivotal role in myocardial inflammation and ischemic injury in animals. RNA profiling has identified that numerous microRNA (miRNAs), such as ss\u2013miR-146a-5p, are upregulated in plasma following myocardial ischemia, and certain uridine-rich miRNAs exhibit strong proinflammatory effects in immune cells via ssRNA-sensing mechanism. However, the effect of extracellular miRNAs on myocardial inflammation and cardiac cell function remains unknown. In this study, we treated adult mouse cardiomyocytes with miR-146a-5p loaded in extracellular vesicles and observed a dose- and TLR7-dependent production of CXCL-2, IL-6, and TNF-\u03b1. In vivo, a single dose of myocardial injection of miR-146a-5p induced both cytokine expression (CXCL2, IL-6, and TNF-\u03b1) and innate immune cell activation (CD45+ leukocytes, Ly6Cmid+ monocytes, Ly6G+ neutrophils), which was significantly attenuated in the hearts of TLR7 KO mice. We discovered that conditioned media from miR-146a\u2013treated macrophages stimulated proinflammatory cytokine production in adult cardiomyocytes and significantly inhibited their sarcomere shortening. Finally, using an electric cell impedance\u2013sensing assay, we found that the conditioned media from miR-146a\u2013treated cardiac fibroblasts or cardiomyocytes impaired the barrier function of coronary artery endothelial cells. Taken together, these data demonstrate that extracellular miR-146a-5p activates multiple cardiac cells and induces myocardial inflammation and cardiomyocyte dysfunction via intercellular interaction and innate immune TLR7 nucleic acid sensing.<\/jats:p>","DOI":"10.4049\/immunohorizons.2000075","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T18:50:11Z","timestamp":1600714211000},"page":"561-572","source":"Crossref","is-referenced-by-count":45,"title":["Extracellular miR-146a-5p Induces Cardiac Innate Immune Response and Cardiomyocyte Dysfunction"],"prefix":"10.1093","volume":"4","author":[{"given":"Briana K","family":"Shimada","sequence":"first","affiliation":[{"name":"Translational Research Program, Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4178-1259","authenticated-orcid":false,"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Translational Research Program, Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Translational Research Program, Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5625-403X","authenticated-orcid":false,"given":"Sheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Translational Research Program, Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4354-6498","authenticated-orcid":false,"given":"Andrew","family":"Suen","sequence":"additional","affiliation":[{"name":"Translational Research Program, Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0267-6146","authenticated-orcid":false,"given":"Stephanie M","family":"Kronstadt","sequence":"additional","affiliation":[{"name":"Fischell Department of Bioengineering, University of Maryland , College Park, MD 20740"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjana","family":"Jeyaram","sequence":"additional","affiliation":[{"name":"Fischell Department of Bioengineering, University of Maryland , College Park, MD 20740"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M","family":"Jay","sequence":"additional","affiliation":[{"name":"Fischell Department of Bioengineering, University of Maryland , College Park, MD 20740"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0820-4246","authenticated-orcid":false,"given":"Lin","family":"Zou","sequence":"additional","affiliation":[{"name":"Translational Research Program, Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2505-1360","authenticated-orcid":false,"given":"Wei","family":"Chao","sequence":"additional","affiliation":[{"name":"Translational Research Program, Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research, University of Maryland School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,22]]},"reference":[{"key":"2025010607444314600_r1","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1056\/NEJMra071667","article-title":"Myocardial reperfusion injury","volume":"357","author":"Yellon","year":"2007","journal-title":"N. 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