{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:14:32Z","timestamp":1790698472584,"version":"4.1.0"},"reference-count":88,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Toxoplasma gondii<\/jats:italic> uracil phosphoribosyltransferase (UPRT) converts 4\u2010thiouracil (4TUc) into 4\u2010thiouridine (4TUd), which is incorporated into nascent RNAs and can be biotinylated, then labelled with streptavidin conjugates or isolated via streptavidin\u2010affinity methods. Here, we generated mice that expressed <jats:italic>T. gondii<\/jats:italic> UPRT only in cardiomyocytes (<jats:sup>CM<\/jats:sup>UPRT mice) and tested our hypothesis that CM\u2010derived miRNAs (<jats:sup>CM<\/jats:sup>miRs) are transferred into remote organs after myocardial infarction (MI) by small extracellular vesicles (sEV) that are released from the heart into the peripheral blood (<jats:sup>PB<\/jats:sup>sEV). We found that 4TUd was incorporated with high specificity and sensitivity into RNAs isolated from the hearts and <jats:sup>PB<\/jats:sup>sEV of <jats:sup>CM<\/jats:sup>UPRT mice 6\u00a0h after 4TUc injection. In <jats:sup>PB<\/jats:sup>sEV, 4TUd was incorporated into CM\u2010specific\/enriched miRs including miR\u2010208a, but not into miRs with other organ or tissue\u2010type specificities. 4TUd\u2010labelled miR208a was also present in lung tissues, especially lung endothelial cells (ECs), and CM\u2010derived miR\u2010208a (<jats:sup>CM<\/jats:sup>miR\u2010208a) levels peaked 12\u00a0h after experimentally induced MI in <jats:sup>PB<\/jats:sup>sEV and 24\u00a0h after MI in the lung. Notably, miR\u2010208a is expressed from intron 29 of \u03b1 myosin heavy chain (\u03b1MHC), but \u03b1MHC transcripts were nearly undetectable in the lung. When <jats:sup>PB<\/jats:sup>sEV from mice that underwent MI (MI\u2010<jats:sup>PB<\/jats:sup>sEV) or sham surgery (Sham\u2010<jats:sup>PB<\/jats:sup>sEV) were injected into intact mice, the expression of Tmbim6 and NLK, which are suppressed by miR\u2010208a and cooperatively regulate inflammation via the NF\u2010\u03baB pathway, was lower in the lungs of MI\u2010<jats:sup>PB<\/jats:sup>sEV\u2013treated animals than the lungs of animals treated with Sham\u2010<jats:sup>PB<\/jats:sup>sEV or saline. In MI mice, Tmbim6 and NLK were downregulated, whereas endothelial adhesion molecules and pro\u2010inflammatory cells were upregulated in the lung; these changes were significantly attenuated when the mice were treated with miR\u2010208a antagomirs prior to MI surgery. Thus, <jats:sup>CM<\/jats:sup>UPRT mice enables us to track <jats:sup>PB<\/jats:sup>sEV\u2010mediated transport of <jats:sup>CM<\/jats:sup>miRs and identify an miR\u2010208a\u2010mediated mechanism by which myocardial injury alters the expression of genes and inflammatory response in the lung.<\/jats:p>","DOI":"10.1002\/jev2.12246","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T10:55:24Z","timestamp":1666004124000},"source":"Crossref","is-referenced-by-count":15,"title":["Metabolic labeling of cardiomyocyte\u2010derived small extracellular\u2010vesicle (sEV) miRNAs identifies miR\u2010208a in cardiac regulation of lung gene expression"],"prefix":"10.1002","volume":"11","author":[{"given":"Chaoshan","family":"Han","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering School of Medicine and School of Engineering University of Alabama at Birmingham  Birmingham Alabama 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