{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:57:37Z","timestamp":1780592257543,"version":"3.54.1"},"reference-count":56,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NEOMED internal funding","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study was to determine whether exosomes from Nicotinamide phosphoribosyltransferase (NAMPT)-overexpressing mesenchymal stem cells (MSC NAMPT-Exo) can attenuate aortic stenosis (AS) and explored the underlying mechanism. NAMPT expression was examined in EC CXCR4 KO (AS) mouse hearts. Six-week-old AS mice received weekly injections of NAMPT-Exo, MSC-Exo, or PBS for three weeks, followed by echocardiography and histological examination of the valves (H&amp;E, Alizarin Red, immunofluorescence). Cardiac ECs from control, AS, and NAMPT-Exo-treated mice were analyzed for miRNA expression (miR-146a-3p\/5p, miR-125b-5p, miR-142a-5p). NAMPT expression was decreased in AS hearts. Treatment with NAMPT-Exo reduced aortic valve peak velocity, valvular thickening, and microcalcifications, while improving ejection fraction, fractional shortening, and ventricular dimensions. AS endothelial cells showed elevated levels of miR-146a-3p, miR-146a-5p, and miR-142a-5p, NAMPT-Exo specifically normalized miR-146a-3p. Histology revealed EndMT in AS valves, which was diminished by NAMPT-Exo. In vitro, inhibiting miR-146a-3p suppressed TGF-\u03b2-induced EndMT. Our results demonstrate that NAMPT-enriched MSC-derived exosomes effectively slow the progression of AS. Additionally, our findings highlight miR-146a-3p as a key regulator of EndMT, suggesting it as a potential molecular target for future therapies.<\/jats:p>","DOI":"10.3390\/ijms27010256","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:50:21Z","timestamp":1766710221000},"page":"256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exosomal NAMPT from Engineered Mesenchymal Stem Cells Mitigates Aortic Stenosis via Metabolic and Anti-Inflammatory Pathways"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9764-7851","authenticated-orcid":false,"given":"Dipan Kumar","family":"Kundu","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA"},{"name":"Department of Biomedical Sciences, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Kiedrowski","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Gadd","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2347-3578","authenticated-orcid":false,"given":"Min","family":"Gao","sequence":"additional","affiliation":[{"name":"Advanced Materials and Liquid Crystal Institute, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Evan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7825-9539","authenticated-orcid":false,"given":"Liya","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1188-6746","authenticated-orcid":false,"given":"Vahagn","family":"Ohanyan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4522-7914","authenticated-orcid":false,"given":"William M.","family":"Chilian","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3557-7099","authenticated-orcid":false,"given":"Feng","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Czarny, M.J., and Resar, J.R. 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