Warfarin, but not rivaroxaban, promotes the calcification of the aortic valve in ApoE-/- mice

Cardiovascular Therapeutics
Marcello RattazziPaolo Pauletto

Abstract

Vitamin K antagonists, such as warfarin, are known to promote arterial calcification through blockade of gamma-carboxylation of Matrix-Gla-Protein. 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. To compare the effect of warfarin and rivaroxaban on the progression of aortic valve calcification in atherosclerotic mice. 42 ApoE-/- mice fed with Western-type Diet (WTD) were randomized to treatment with warfarin (n = 14), rivaroxaban (n = 14) or control (n = 14) for 8 weeks. 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 WTD alone (P = .025) or rivaroxaban (P = .005), whereas no significant differences were found between rivaroxaban and WTD (P = .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 bovi...Continue Reading

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Citations

Jul 22, 2019·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Pablo Ureña-TorresJordi Bover
Jan 29, 2019·Journal of Nephrology·Kelvin Cheuk-Wai Leung, Jennifer Marie MacRae
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