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Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats.

Author(s): Schurgers LJ, Spronk HM, Soute BA, Schiffers PM, Demey JG, Vermeer C

Affiliation(s): Cardiovascular Research Institute (CARIM), Maastricht University, Maastricht, Netherlands.

Publication date & source: 2006-11-30, Blood., [Epub ahead of print]

Arterial calcification (AC) is generally regarded as an independent risk factor for cardiovascular morbidity and mortality. Matrix Gla-protein (MGP) is a potent inhibitor of AC and its activity depends on vitamin K (VK). In rats, inactivation of MGP by treatment with the vitamin K-antagonist warfarin leads to rapid calcification of the arteries. Here we investigated whether pre-formed AC can be regressed by a VK-rich diet. Rats received a calcification-inducing diet containing both VK and warfarin (W&K). During a second 6-week period, animals were randomized to receive either W&K (3.0 mg/g & 1.5 mg/g, subsequently), a diet containing normal (5 microg/g) or high (100 microg/g) amount of VK (either K1 or K2). Increased aortic calcium concentration was observed in the group that continued to receive W&K, and also in the group changed to the normal dose of VK, AC progressed. Both the VK-rich diets decreased the arterial calcium content by some 50%. Additionally, arterial distensibility was restored by the VK-rich diet. Using MGP antibodies, local VK-deficiency was demonstrated at sites of calcification. This is the first study in rats demonstrating that AC and the resulting decreased arterial distensibility are reversible by high VK intake.

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