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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2823-2831. Prepublished online as a Blood First Edition Paper on November 30, 2006; DOI 10.1182/blood-2006-07-035345. This Article Full Text (PDF) All Versions of this Article: blood-2006-07-035345v1 109/7/2823    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Schurgers, L. J Articles by Vermeer, C. Search for Related Content PubMed PubMed Citation Articles by Schurgers, L. J Articles by Vermeer, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 14, 2006 Accepted November 16, 2006 Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats Leon J Schurgers*, Henri M.H Spronk, Berry A.M Soute, Paul M Schiffers, Jo GR DeMey, and Cees Vermeer Cardiovascular Research Institute (CARIM), Maastricht University, Maastricht, Netherlands Dept of Internal Medicine, CARIM, Maastricht University, Maastricht, Netherlands Dept of Pharmacology & Toxicology, CARIM, Maastricht University, Maastricht, Netherlands VitaK, Maastricht University, Maastricht, Netherlands * Corresponding author; email: l.schurgers{at}bioch.unimaas.nl. 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 µg/g) or high (100 µg/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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. D. Parker, J. H. Ix, E. C. M. Cranenburg, C. Vermeer, M. A. Whooley, and L. J. Schurgers Association of kidney function and uncarboxylated matrix Gla protein: Data from the Heart and Soul Study Nephrol. Dial. Transplant., July 1, 2009; 24(7): 2095 - 2101. [Abstract] [Full Text] [PDF] M K. Shea, C. J O'Donnell, U. Hoffmann, G. E Dallal, B. Dawson-Hughes, J. M Ordovas, P. A Price, M. K Williamson, and S. L Booth Vitamin K supplementation and progression of coronary artery calcium in older men and women Am. J. Clinical Nutrition, June 1, 2009; 89(6): 1799 - 1807. [Abstract] [Full Text] [PDF] R. Westenfeld, C. Schafer, T. Kruger, C. Haarmann, L. J. Schurgers, C. Reutelingsperger, O. Ivanovski, T. Drueke, Z. A. Massy, M. Ketteler, et al. Fetuin-A Protects against Atherosclerotic Calcification in CKD J. Am. Soc. Nephrol., June 1, 2009; 20(6): 1264 - 1274. [Abstract] [Full Text] [PDF] Q. Li, L. J. Schurgers, A. C.M. Smith, M. Tsokos, J. Uitto, and E. W. Cowen Co-Existent Pseudoxanthoma Elasticum and Vitamin K-Dependent Coagulation Factor Deficiency: Compound Heterozygosity for Mutations in the GGCX Gene Am. J. Pathol., February 1, 2009; 174(2): 534 - 540. [Abstract] [Full Text] [PDF] L. L. Demer and Y. Tintut Vascular Calcification: Pathobiology of a Multifaceted Disease Circulation, June 3, 2008; 117(22): 2938 - 2948. [Full Text] [PDF] M. Teichert, L.E. Visser, R.H.N. van Schaik, A. Hofman, A.G. Uitterlinden, P.A.G. M. De Smet, J.C.M. Witteman, and B.H.Ch. Stricker Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1) Polymorphism and Aortic Calcification: The Rotterdam Study Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): 771 - 776. [Abstract] [Full Text] [PDF] M. J. H. van Summeren, W. G. M. Spliet, A. van Royen-Kerkhof, C. Vermeer, M. Lilien, W. Kuis, and L. J. Schurgers Calcinosis in juvenile dermatomyositis: a possible role for the vitamin K-dependent protein matrix Gla protein Rheumatology, March 1, 2008; 47(3): 267 - 271. [Abstract] [Full Text] [PDF] D. A. Towler Vascular Calcification: A Perspective On An Imminent Disease Epidemic IBMS BoneKEy, February 1, 2008; 5(2): 41 - 58. [Abstract] [Full Text] [PDF]

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