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Thromb Res. 2008;122(3):411-7. doi: 10.1016/j.thromres.2007.12.005. Epub 2008 Jan 30.

Effects of the blood coagulation vitamin K as an inhibitor of arterial calcification.

Author information

  • 1Department of Internal Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA. rwallin@wfubmc.edu

Abstract

INTRODUCTION:

The transformation of smooth muscle cells (VSMCs) in the vessel wall to osteoblast like cells is known to precede arterial calcification which may cause bleeding complications. The vitamin K-dependent protein MGP has been identified as an inhibitor of this process by binding BMP-2, a growth factor known to trigger the transformation. In this study, we determined if the vitamin K-dependent Gla region in MGP by itself can inhibit the growth factor activity of BMP-2 and if menaquinone-4 (MK4) regulates gene expression in VSMCs.

MATERIALS AND METHODS:

A synthetic gamma-carboxyglutamic acid (Gla) containing peptide covering the Gla region in human MGP was used to test its ability to inhibit BMP-2 induced transformation of mouse pro-myoblast C2C12 cells into osteoblasts. MK4 was tested by microarray analysis as a gene regulatory molecule in VSMCs.

RESULTS AND CONCLUSIONS:

The results show that the Gla - but not the Glu-peptide inhibited the transformation which provide evidence that the Gla region in MGP is directly involved in the BMP-2/MGP interaction and emphasizes the importance of the vitamin K-dependent modification of MGP. From the data obtained from the microarray analysis, we focused on two quantitatively altered cDNAs representing proteins known to be associated with vessel wall calcification. DT-diaphorase of the vitamin K-cycle, showed increased gene expression with a 4.8-fold higher specific activity in MK4 treated cells. Osteoprotegrin gene expression was down regulated and osteoprotegrin protein secretion from the MK4 treated cells was lowered to 1.8-fold. These findings suggest that MK4 acts as an anti-calcification component in the vessel wall.

PMID:
18234293
[PubMed - indexed for MEDLINE]
PMCID:
PMC2529147
Free PMC Article

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