{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:47:18Z","timestamp":1791175638763,"version":"4.1.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Vascular calcification is an independent risk factor for cardiovascular disease. Once thought to be a passive process, vascular calcification is now known to be actively prevented by proteins acting systemically (fetuin-A) or locally (matrix Gla protein). Warfarin is a vitamin K antagonist, widely prescribed to reduce coagulation by inhibiting vitamin K\u2013dependent coagulation factors. Recently, it became clear that vitamin K antagonists also affect vascular calcification by inactivation of matrix Gla protein. Here, we investigated functional cardiovascular characteristics in a mouse model with warfarin-induced media calcification.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>DBA\/2 mice received diets with variable concentrations of warfarin (0.03, 0.3, and 3 mg\/g) with vitamin K1 at variable time intervals (1, 4, and 7 weeks). Von Kossa staining revealed that warfarin treatment induced calcified areas in both medial layer of aorta and heart in a dose- and time-dependent fashion, which could be inhibited by simultaneous vitamin K2 treatment. With ongoing calcification, matrix Gla protein mRNA expression decreased, and inactive matrix Gla protein expression increased. TdT-mediated dUTP-biotin nick end labeling\u2013positive apoptosis increased, and vascular smooth muscle cell number was concomitantly reduced by warfarin treatment. On a functional level, warfarin treatment augmented aortic peak velocity, aortic valve\u2013peak gradient, and carotid pulse-wave velocity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\u2014<\/jats:title>\n            <jats:p>Warfarin induced significant calcification with resulting functional cardiovascular damage in DBA\/2 wild-type mice. The model would enable future researchers to decipher mechanisms of vascular calcification and may guide them in the development of new therapeutic strategies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.113.302244","type":"journal-article","created":{"date-parts":[[2013,8,30]],"date-time":"2013-08-30T04:32:03Z","timestamp":1377837123000},"page":"2618-2624","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":90,"title":["Warfarin Induces Cardiovascular Damage in Mice"],"prefix":"10.1161","volume":"33","author":[{"given":"Thilo","family":"Kr\u00fcger","sequence":"first","affiliation":[{"name":"From the Department of Nephrology, University Hospital of the Rheinisch Westf\u00e4lische Technische Hochschule Aachen, Aachen, Germany (T.K., S.O., N.K., P.B., G.S., V.M.B., J.F.); Department of Biochemistry, Cardiovascular Research Institute CARIM, University of Maastricht, Maastricht, The Netherlands (L.J.S.); Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University D\u00fcsseldorf, D\u00fcsseldorf, Germany (A.M.v.d.S., V.V., R.W.); Department of Pathology, University Hospital of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Oelenberg","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, University Hospital of the Rheinisch Westf\u00e4lische Technische Hochschule Aachen, Aachen, Germany (T.K., S.O., N.K., P.B., G.S., V.M.B., J.F.); Department of Biochemistry, Cardiovascular Research Institute CARIM, University of Maastricht, Maastricht, The Netherlands (L.J.S.); Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University D\u00fcsseldorf, D\u00fcsseldorf, Germany (A.M.v.d.S., V.V., R.W.); Department of Pathology, University Hospital of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Kaesler","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, University Hospital of the Rheinisch Westf\u00e4lische Technische Hochschule Aachen, Aachen, Germany (T.K., S.O., N.K., P.B., G.S., V.M.B., J.F.); Department of Biochemistry, Cardiovascular Research Institute CARIM, University of Maastricht, Maastricht, The Netherlands (L.J.S.); Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University D\u00fcsseldorf, D\u00fcsseldorf, Germany (A.M.v.d.S., V.V., R.W.); Department of Pathology, University Hospital of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon J.","family":"Schurgers","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, University Hospital of the Rheinisch Westf\u00e4lische Technische Hochschule Aachen, Aachen, Germany (T.K., S.O., N.K., P.B., G.S., V.M.B., J.F.); Department of Biochemistry, Cardiovascular Research Institute CARIM, University of Maastricht, Maastricht, The Netherlands (L.J.S.); Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University D\u00fcsseldorf, D\u00fcsseldorf, Germany (A.M.v.d.S., V.V., R.W.); Department of Pathology, University Hospital of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette M.","family":"van de Sandt","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, University Hospital of the Rheinisch Westf\u00e4lische Technische Hochschule Aachen, Aachen, Germany (T.K., S.O., N.K., P.B., G.S., V.M.B., J.F.); Department of Biochemistry, Cardiovascular Research Institute CARIM, University of Maastricht, Maastricht, The Netherlands (L.J.S.); Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University D\u00fcsseldorf, D\u00fcsseldorf, Germany (A.M.v.d.S., V.V., R.W.); Department of Pathology, University Hospital of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Boor","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, University Hospital of the Rheinisch Westf\u00e4lische Technische Hochschule Aachen, Aachen, Germany (T.K., S.O., N.K., P.B., G.S., V.M.B., J.F.); Department of Biochemistry, Cardiovascular Research Institute CARIM, University of Maastricht, Maastricht, The Netherlands (L.J.S.); Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University D\u00fcsseldorf, D\u00fcsseldorf, Germany (A.M.v.d.S., V.V., R.W.); Department of Pathology, University Hospital of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Schlieper","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, University Hospital of the Rheinisch Westf\u00e4lische Technische Hochschule Aachen, Aachen, Germany (T.K., S.O., N.K., P.B., G.S., V.M.B., J.F.); Department of Biochemistry, Cardiovascular Research Institute CARIM, University of Maastricht, Maastricht, The Netherlands (L.J.S.); Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University D\u00fcsseldorf, D\u00fcsseldorf, Germany (A.M.v.d.S., V.V., R.W.); Department of Pathology, University Hospital of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent M.","family":"Brandenburg","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, University Hospital of the Rheinisch Westf\u00e4lische Technische Hochschule Aachen, Aachen, Germany (T.K., S.O., N.K., P.B., G.S., V.M.B., J.F.); Department of Biochemistry, Cardiovascular Research Institute CARIM, University of Maastricht, Maastricht, The Netherlands (L.J.S.); Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University D\u00fcsseldorf, D\u00fcsseldorf, Germany (A.M.v.d.S., V.V., R.W.); Department of Pathology, University Hospital of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertalan C.","family":"Fekete","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, University Hospital of the Rheinisch Westf\u00e4lische Technische Hochschule Aachen, Aachen, Germany (T.K., S.O., N.K., P.B., G.S., V.M.B., J.F.); Department of Biochemistry, Cardiovascular Research Institute CARIM, University of Maastricht, Maastricht, The Netherlands (L.J.S.); Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University D\u00fcsseldorf, D\u00fcsseldorf, Germany (A.M.v.d.S., V.V., R.W.); Department of Pathology, University Hospital of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Veulemans","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, University Hospital of the Rheinisch Westf\u00e4lische Technische Hochschule Aachen, Aachen, Germany (T.K., S.O., N.K., P.B., G.S., V.M.B., J.F.); Department of Biochemistry, Cardiovascular Research Institute CARIM, University of Maastricht, Maastricht, The Netherlands (L.J.S.); Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University D\u00fcsseldorf, D\u00fcsseldorf, Germany (A.M.v.d.S., V.V., R.W.); Department of Pathology, University Hospital of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Ketteler","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, University Hospital of the Rheinisch Westf\u00e4lische Technische Hochschule Aachen, Aachen, Germany (T.K., S.O., N.K., P.B., G.S., V.M.B., J.F.); Department of Biochemistry, Cardiovascular Research Institute CARIM, University of Maastricht, Maastricht, The Netherlands (L.J.S.); Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University D\u00fcsseldorf, D\u00fcsseldorf, Germany (A.M.v.d.S., V.V., R.W.); Department of Pathology, University Hospital of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cees","family":"Vermeer","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, University Hospital of the Rheinisch Westf\u00e4lische Technische Hochschule Aachen, Aachen, Germany (T.K., S.O., N.K., P.B., G.S., V.M.B., J.F.); Department of Biochemistry, Cardiovascular Research Institute CARIM, University of Maastricht, Maastricht, The Netherlands (L.J.S.); Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University D\u00fcsseldorf, D\u00fcsseldorf, Germany (A.M.v.d.S., V.V., R.W.); Department of Pathology, University Hospital of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willi","family":"Jahnen-Dechent","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, University Hospital of the Rheinisch Westf\u00e4lische Technische Hochschule Aachen, Aachen, Germany (T.K., S.O., N.K., P.B., G.S., V.M.B., J.F.); Department of Biochemistry, Cardiovascular Research Institute CARIM, University of Maastricht, Maastricht, The Netherlands (L.J.S.); Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University D\u00fcsseldorf, D\u00fcsseldorf, Germany (A.M.v.d.S., V.V., R.W.); Department of Pathology, University Hospital of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Floege","sequence":"additional","affiliation":[{"name":"From the Department of Nephrology, University Hospital of the Rheinisch Westf\u00e4lische Technische Hochschule Aachen, Aachen, Germany (T.K., S.O., N.K., P.B., G.S., V.M.B., J.F.); Department of Biochemistry, Cardiovascular Research Institute CARIM, University of Maastricht, Maastricht, The Netherlands (L.J.S.); Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University D\u00fcsseldorf, D\u00fcsseldorf, Germany (A.M.v.d.S., V.V., R.W.); Department of Pathology, University 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