Role of vitamin K and vitamin K-dependent proteins in vascular calcification

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. Vitamin K has a key function in the synthesis of at least two proteins involved in...

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Bibliographic Details
Published in:	Clinical research in cardiology Vol. 90 Suppl 3; pp. 57 - 63
Main Authors:	Schurgers, L J, Dissel, P E, Spronk, H M, Soute, B A, Dhore, C R, Cleutjens, J P, Vermeer, C
Format:	Journal Article
Language:	English
Published:	Germany Springer Nature B.V 01-04-2001
Subjects:	Accumulation Arteriosclerosis Arteriosclerosis - pathology Atherosclerosis Biomedical materials Blood vessels Bone turnover Calcification Calcification (ectopic) Calcinosis - pathology Calcium Calcium - metabolism Calcium-Binding Proteins - metabolism Carboxylation Coagulation Consumption Diabetes mellitus Extracellular Matrix Proteins Food intake Human performance Humans Matrix Gla Protein Menaquinones Monoclonal antibodies Muscle, Smooth, Vascular - pathology Osteocalcin Osteocalcin - metabolism Phylloquinone Protein turnover Proteins Quinones Risk analysis Risk factors Synthesis Tissues Vascular tissue Vitamin K Vitamin K - physiology Vitamin K 1 - physiology Warfarin
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Summary:	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. 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. 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. 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. 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.
ISSN:	0300-5860 1861-0684 1861-0692
DOI:	10.1007/s003920170043