Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats.
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 preformed 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 randomly assigned to receive either W&K (3.0 mg/g and 1.5 mg/g, subsequently), a diet containing a 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 and AC progressed. Both the VK-rich diets decreased the arterial calcium content by some 50%. In addition, 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.
Schurgers
Leon J
LJ
Cardiovascular Research Institute (CARIM), Maastricht University, The Netherlands. l.schurgers@bioch.unimaas.nl
Spronk
Henri M H
HM
Soute
Berry A M
BA
Schiffers
Paul M
PM
DeMey
Jo G R
JG
Vermeer
Cees
C
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001158:Arteries / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D001696:Biomechanical Phenomena; D002114:Calcinosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D014812:Vitamin K / Q000008:administration & dosage* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014859:Warfarin / Q000008:administration & dosage / Q000633:toxicity*; D000097568:Matrix Gla Protein
D002118:Calcium; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D014812:Vitamin K; D014859:Warfarin; D000097568:Matrix Gla Protein