Warfarin(Coumadin) Vitamin K antagonist prescribed for heart patients causes rapid calcification in rat arteries and heart valves.

January 24, 2003

743228 & dopt=Abstract

Warfarin causes rapid calcification of the elastic lamellae in rat arteries and

heart valves.

Price PA, Faus SA, Williamson MK.

Department of Biology, University of California, San Diego, La Jolla 92093-0368,

USA. pprice

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 gamma-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.

PMID: 9743228 [PubMed - indexed for MEDLINE]

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