Arteriosclerosis, Thrombosis, and Vascular Biology. 1998;18:1400-1407
© 1998 American Heart Association, Inc.
Original Contributions |
Warfarin Causes Rapid Calcification of the Elastic Lamellae in Rat Arteries and Heart Valves
From the Department of Biology, University of California, San Diego, La Jolla, Calif.
Correspondence to Dr Paul A. Price, Department of Biology, 0368, University of California, San Diego, La Jolla, CA 92093-0368. E-mail pprice{at}ucsd.edu
Abstract—High doses of warfarin
cause focal calcification of the elastic lamellae in the media of major
arteries and in aortic heart valves in the rat. Aortic calcification
was first seen after 2 weeks of warfarin treatment and progressively
increased in density at 3, 4, and 5 weeks of treatment. By 5 weeks, the
highly focal calcification of major arteries could be seen on
radiographs and by visual inspection of the artery. The calcification
of arteries induced by warfarin is similar to that seen in the matrix
Gla protein (MGP)–deficient mouse, which suggests that warfarin
induces artery calcification by inhibiting 
-carboxylation of MGP and
thereby inactivating the putative calcification-inhibitory
activity of the protein. Warfarin treatment markedly increased the
levels of MGP mRNA and protein in calcifying arteries and decreased the
level of MGP in serum. Warfarin treatment did not affect bone growth,
overall weight gain, or serum calcium and phosphorus levels, and,
because of the concurrent administration of vitamin K, prothrombin
times and hematocrits were normal. The results indicate that the
improved warfarin plus vitamin K treatment protocol developed in this
study should provide a useful model to investigate the role of MGP in
preventing calcification of arteries and heart valves.
Key Words: matrix Gla protein • warfarin • vitamin K • artery calcification • heart valve calcification
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