Role of vitamin K and vitamin K-dependent proteins in vascular calcification.
OBJECTIVE
To provide a rational basis for recommended daily allowances (RDA) of dietary phylloquinone (vitamin K1) and menaquinone (vitamin K2) intake that adequately supply extrahepatic (notably vascular) tissue requirements.


BACKGROUND
Vitamin K has a key function in the synthesis of at least two proteins involved in calcium and bone metabolism, namely osteocalcin and matrix Gla-protein (MGP). MGP was shown to be a strong inhibitor of vascular calcification. Present RDA values for vitamin K are based on the hepatic phylloquinone requirement for coagulation factor synthesis. Accumulating data suggest that extrahepatic tissues such as bone and vessel wall require higher dietary intakes and have a preference for menaquinone rather than for phylloquinone.


METHODS
Tissue-specific vitamin K consumption under controlled intake was determined in warfarin-treated rats using the vitamin K-quinone/epoxide ratio as a measure for vitamin K consumption. Immunohistochemical analysis of human vascular material was performed using a monoclonal antibody against MGP. The same antibody was used for quantification of MGP levels in serum.


RESULTS
At least some extrahepatic tissues including the arterial vessel wall have a high preference for accumulating and using menaquinone rather than phylloquinone. Both intima and media sclerosis are associated with high tissue concentrations of MGP, with the most prominent accumulation at the interface between vascular tissue and calcified material. This was consistent with increased concentrations of circulating MGP in subjects with atherosclerosis and diabetes mellitus.


CONCLUSIONS
This is the first report demonstrating the association between MGP and vascular calcification. The hypothesis is put forward that undercarboxylation of MGP is a risk factor for vascular calcification and that the present RDA values are too low to ensure full carboxylation of MGP.
Schurgers
L J
LJ
Department of Biochemistry, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Dissel
P E
PE
Spronk
H M
HM
Soute
B A
BA
Dhore
C R
CR
Cleutjens
J P
JP
Vermeer
C
C
D001161:Arteriosclerosis / Q000473:pathology*; D002114:Calcinosis / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D015675:Osteocalcin / Q000378:metabolism; D014812:Vitamin K / Q000502:physiology*; D010837:Vitamin K 1 / Q000502:physiology*; D000097568:Matrix Gla Protein
D002118:Calcium; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D015675:Osteocalcin; D014812:Vitamin K; D010837:Vitamin K 1; D000097568:Matrix Gla Protein