{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T14:42:40Z","timestamp":1774536160843,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,6,28]],"date-time":"2018-06-28T00:00:00Z","timestamp":1530144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Vitamin K antagonists, such as warfarin, are known to promote arterial calcification through blockade of gamma\u2010carboxylation of Matrix\u2010Gla\u2010Protein. It is currently unknown whether other oral anticoagulants such as direct inhibitors of Factor Xa can have protective effects on the progression of aortic valve calcification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To compare the effect of warfarin and rivaroxaban on the progression of aortic valve calcification in atherosclerotic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>42 ApoE\u2212\/\u2212 mice fed with Western\u2010type Diet (<jats:styled-content style=\"fixed-case\">WTD<\/jats:styled-content>) were randomized to treatment with warfarin (n\u00a0=\u00a014), rivaroxaban (n\u00a0=\u00a014) or control (n\u00a0=\u00a014) for 8\u00a0weeks. Histological analyses were performed to quantify the calcification of aortic valve leaflets and the development of atherosclerosis. The analyses showed a significant increase in valve calcification in mice treated with warfarin as compared to <jats:styled-content style=\"fixed-case\">WTD<\/jats:styled-content> alone (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.025) or rivaroxaban (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.005), whereas no significant differences were found between rivaroxaban and <jats:styled-content style=\"fixed-case\">WTD<\/jats:styled-content> (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.35). Quantification of atherosclerosis and intimal calcification was performed on the innominate artery of the mice and no differences were found between the 3 treatments as far as atherogenesis and calcium deposition is concerned. In vitro experiments performed using bovine interstitial valve cells (<jats:styled-content style=\"fixed-case\">VIC<\/jats:styled-content>) showed that treatment with rivaroxaban did not prevent the osteogenic conversion of the cells but reduce the over\u2010expression of <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102 induced by inflammatory mediators.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We showed that warfarin, but not rivaroxaban, could induce calcific valve degeneration in a mouse model of atherosclerosis. Both the treatments did not significantly affect the progression of atherosclerosis. Overall, these data suggest a safer profile of rivaroxaban on the risk of cardiovascular disease progression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1755-5922.12438","type":"journal-article","created":{"date-parts":[[2018,5,30]],"date-time":"2018-05-30T15:14:05Z","timestamp":1527693245000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Warfarin, but not rivaroxaban, promotes the calcification of the aortic valve in ApoE\u2212\/\u2212 mice"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3437-7263","authenticated-orcid":false,"given":"Marcello","family":"Rattazzi","sequence":"first","affiliation":[{"name":"Department of Medicine \u2010 DIMED University of Padova  Padova Italy"},{"name":"Medicina Generale I^ Ca\u2019 Foncello Hospital  Treviso Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Faggin","sequence":"additional","affiliation":[{"name":"Department of Medicine \u2010 DIMED University of Padova  Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Bertacco","sequence":"additional","affiliation":[{"name":"Department of Medicine \u2010 DIMED University of Padova  Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Nardin","sequence":"additional","affiliation":[{"name":"Department of Medicine \u2010 DIMED University of Padova  Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leopoldo","family":"Pagliani","sequence":"additional","affiliation":[{"name":"ORAS Rehabilitation Hospital  Motta di Livenza, Treviso Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Plebani","sequence":"additional","affiliation":[{"name":"Department of Medicine \u2010 DIMED University of Padova  Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Cinetto","sequence":"additional","affiliation":[{"name":"Department of Medicine \u2010 DIMED University of Padova  Padova Italy"},{"name":"Medicina Generale I^ Ca\u2019 Foncello Hospital  Treviso Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Guidolin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Padova  Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Puato","sequence":"additional","affiliation":[{"name":"Department of Medicine \u2010 DIMED University of Padova  Padova Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Pauletto","sequence":"additional","affiliation":[{"name":"ORAS Rehabilitation Hospital  Motta di Livenza, Treviso Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,6,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-013-9712-z"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.090860"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2014.10.021"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.174342"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000166600.58468.1b"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr100682g"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.302523"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2012.12.008"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2015.11.032"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/clc.20865"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02758.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016060651"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt112"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2016.04.008"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00553.2016"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep35580"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/432080"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2015.03.023"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0049-3848(87)90212-X"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.18.9.1400"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.10.027"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25714"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043229"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATV.0000000000000062"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvs325"}],"container-title":["Cardiovascular Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1755-5922.12438","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1755-5922.12438","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T10:58:51Z","timestamp":1694948331000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1755-5922.12438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,28]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,8]]}},"alternative-id":["10.1111\/1755-5922.12438"],"URL":"https:\/\/doi.org\/10.1111\/1755-5922.12438","archive":["Portico"],"relation":{},"ISSN":["1755-5914","1755-5922"],"issn-type":[{"value":"1755-5914","type":"print"},{"value":"1755-5922","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,28]]},"assertion":[{"value":"2018-03-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12438"}}