{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T09:37:55Z","timestamp":1784281075967,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009045","name":"Uniwersytet Jagiello\u0144ski Collegium Medicum","doi-asserted-by":"publisher","award":["N\/41\/DBS\/000350"],"award-info":[{"award-number":["N\/41\/DBS\/000350"]}],"id":[{"id":"10.13039\/100009045","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2025,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Direct oral anticoagulants (\n DOACs<\/jats:styled-content>\n ) inhibited calcification and extracellular matrix remodelling in valve interstitial cells (\n VICs<\/jats:styled-content>\n ). We assessed whether\n DOACs<\/jats:styled-content>\n affect inflammation and calcification both in\u00a0vitro and in stenotic aortic valves from patients with severe aortic stenosis (\n AS<\/jats:styled-content>\n ). We enrolled 52 patients with\n AS<\/jats:styled-content>\n , including 22 with concomitant atrial fibrillation taking\n DOACs<\/jats:styled-content>\n . Stenotic leaflets obtained during surgery were assessed for osteocalcin and bone morphogenetic protein 4 (\n BMP<\/jats:styled-content>\n \u20104) by immunostaining. Serum interleukin\u20106 (\n IL<\/jats:styled-content>\n \u20106), transforming growth factor\u2010\u03b2 (\n TGF<\/jats:styled-content>\n \u2010\u03b2) and matrix metalloproteinase\u20109 (\n MMP<\/jats:styled-content>\n \u20109) were measured by\n ELISA<\/jats:styled-content>\n . In\u00a0vitro,\n VICs<\/jats:styled-content>\n were treated with rivaroxaban (1 or 10\u2009\u03bcg\/mL) to evaluate\n BMP<\/jats:styled-content>\n \u20104 and nuclear factor kappa B (\n NF<\/jats:styled-content>\n \u2010\n \u03baB<\/jats:styled-content>\n ) expression via immunofluorescence. A median of\n DOAC<\/jats:styled-content>\n therapy was 29.5 [\n Q1<\/jats:styled-content>\n \u2010\n Q3<\/jats:styled-content>\n 20\u201348] months. The percentage of valvular osteocalcin, but not\n BMP<\/jats:styled-content>\n \u20104 positive areas, was 39.6% lower in patients taking\n DOACs<\/jats:styled-content>\n compared to the remainder (16.3%\u2009\u00b1\u20094.8% vs. 27%\u2009\u00b1\u20096.3%,\n p<\/jats:italic>\n \u2009<\u20090.0001). Importantly, both valvular\n BMP<\/jats:styled-content>\n \u20104 and osteocalcin expression correlated inversely with the duration of\n DOAC<\/jats:styled-content>\n therapy (\n r<\/jats:italic>\n \u2009=\u2009\u22120.92 and\n r<\/jats:italic>\n \u2009=\u2009\u22120.78, both\n p<\/jats:italic>\n \u2009<\u20090.0001). Additionally,\n DOAC<\/jats:styled-content>\n \u2010treated patients had lower serum\n MMP<\/jats:styled-content>\n \u20109 (\u221258.1%,\n p<\/jats:italic>\n \u2009<\u20090.0001) and\n TGF<\/jats:styled-content>\n \u2010\u03b2 (\u22127.9%,\n p<\/jats:italic>\n \u2009=\u20090.026) but not\n IL<\/jats:styled-content>\n \u20106 (\n p<\/jats:italic>\n \u2009=\u20090.092) compared to the non\u2010\n DOAC<\/jats:styled-content>\n group.\n DOAC<\/jats:styled-content>\n duration correlated with\n MMP<\/jats:styled-content>\n \u20109 (\n r<\/jats:italic>\n \u2009=\u2009\u22120.89,\n p<\/jats:italic>\n \u2009<\u20090.0001) and\n IL<\/jats:styled-content>\n \u20106 (\n r<\/jats:italic>\n \u2009=\u2009\u22120.63,\n p<\/jats:italic>\n \u2009=\u20090.0015) levels. In\u00a0vitro, rivaroxaban reduced\n NF<\/jats:styled-content>\n \u2010\n \u03baB<\/jats:styled-content>\n and\n BMP<\/jats:styled-content>\n \u20104 expression in\n VICs<\/jats:styled-content>\n in a time\u2010dependent manner (all\n p<\/jats:italic>\n \u2009<\u20090.01), regardless of dose. We showed that\n DOACs,<\/jats:styled-content>\n in a time\u2010dependent manner, exert anti\u2010inflammatory and anti\u2010calcific effects within aortic stenotic valves and in\u00a0vitro in\n VICs<\/jats:styled-content>\n , suggesting long\u2010term\n DOAC<\/jats:styled-content>\n therapy benefits.\n <\/jats:p>","DOI":"10.1111\/jcmm.70927","type":"journal-article","created":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T03:34:47Z","timestamp":1761968087000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Duration\u2010Dependent Effects of Rivaroxaban on Inflammation and Valve Calcification in Aortic Stenosis: Clinical and In\u00a0Vitro Insights"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4026-8971","authenticated-orcid":false,"given":"Magdalena","family":"Kopytek","sequence":"first","affiliation":[{"name":"Department of Thromboembolic Disorders Institute of Cardiology, Jagiellonian University Medical College Krakow Poland"},{"name":"Krakow Centre for Medical Research and Technologies St. John Paul II Hospital Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Zuwa\u0142a","sequence":"additional","affiliation":[{"name":"Students' Scientific Group of Thromboembolic Disorders Jagiellonian University Medical College Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rados\u0142aw","family":"Chudy","sequence":"additional","affiliation":[{"name":"Students' Scientific Group of Thromboembolic Disorders Jagiellonian University Medical College Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weronika","family":"W\u0142\u00f3czyk","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine St. John Paul II Hospital Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Z\u0105bczyk","sequence":"additional","affiliation":[{"name":"Department of Thromboembolic Disorders Institute of Cardiology, Jagiellonian University Medical College Krakow Poland"},{"name":"Krakow Centre for Medical Research and Technologies St. John Paul II Hospital Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Pi\u0105tek","sequence":"additional","affiliation":[{"name":"St. John Paul II Hospital Krak\u00f3w Poland"},{"name":"Department of Cardiovascular Surgery and Transplantology, Institute of Cardiology Jagiellonian University Medical College Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anetta","family":"Undas","sequence":"additional","affiliation":[{"name":"Department of Thromboembolic Disorders Institute of Cardiology, Jagiellonian University Medical College Krakow Poland"},{"name":"Krakow Centre for 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