{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:16:18Z","timestamp":1793834178889,"version":"4.6.1"},"reference-count":66,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,24]],"date-time":"2024-11-24T00:00:00Z","timestamp":1732406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["R01HL114541"],"award-info":[{"award-number":["R01HL114541"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"John L. Locke Jr. Charitable Trust","award":["R01HL114541"],"award-info":[{"award-number":["R01HL114541"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Atherosclerosis is caused by the accumulation of cholesterol within intimal smooth muscle cells (SMCs) and macrophages. However, the transporter ATP-binding cassette subfamily A, member 1 (ABCA1), can remove cholesterol from these intimal, cells reducing atherosclerosis. Antagomir-mediated inhibition of miR-33a-5p, a microRNA that represses ABCA1 translation, promotes ABCA1-dependent cholesterol efflux and may impede atherosclerosis development. In our previous work, transducing cultured endothelial cells (ECs) with a helper-dependent adenoviral vector (HDAd) that expresses X-motif-tagged anti-miR-33a-5p enhanced antagomir packaging into EC-derived exosomes, which delivered the antagomir to cultured SMCs and macrophages. In this present study, we tested whether in vivo transduction of rabbit carotid artery endothelium can deliver an X-motif-tagged anti-miR-33a-5p to subendothelial cells. Rabbit carotid endothelial cells were transduced in vivo with an HDAd expressing anti-miR-33a-5p either with or without the X-motif (n = 11 arteries per vector). Contralateral carotids received HDAd that express scrambled oligonucleotides. Three days after transduction, the antagomir\u2014without the X-motif\u2014was detected in the intima but not in the media of transduced carotids (p = 0.062). The X-motif antagomir was detected in 82% of the intimal extracts (9 out of 11 carotids) and 27% of medial samples (3 out of 11 carotids, p = 0.031). However, the X-motif did not significantly enhance antagomir delivery to the media (p = 0.214 vs. non-X-motif antagomir). Expression of the antagomirs\u2014with and without the X-motif\u2014was sub-stoichiometric in ECs and SMCs. No antagomir-related changes in miR-33a-5p or ABCA1 expressions were detected. Despite its potential as a therapeutic strategy, our exosome-targeted gene transfer system requires further improvements to enhance antagomir expression and delivery to the subendothelial cells.<\/jats:p>","DOI":"10.3390\/biology13120965","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T11:25:33Z","timestamp":1732533933000},"page":"965","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exosome-Mediated Transfer of X-Motif-Tagged Anti-MiR-33a-5p Antagomirs to the Medial Cells of Transduced Rabbit Carotid Arteries"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4463-5211","authenticated-orcid":false,"given":"Goren","family":"Saenz-Pipaon","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Cardiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley K.","family":"Wacker","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianxiang","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0162-8521","authenticated-orcid":false,"given":"Alexis","family":"Stamatikos","sequence":"additional","affiliation":[{"name":"Department of Food, Nutrition, and Packaging Sciences, Clemson University, Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Dichek","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4019","DOI":"10.1093\/eurheartj\/ehae466","article-title":"European Society of Cardiology: The 2023 Atlas of Cardiovascular Disease Statistics","volume":"45","author":"Timmis","year":"2024","journal-title":"Eur. 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