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Thromb Haemost 1999; 82(06): 1764-1767
DOI: 10.1055/s-0037-1614911
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Matrix Gla Protein Synthesis and Gamma-carboxylation in the Aortic Vessel Wall and Proliferating Vascular Smooth Muscle Cells

A Cell System which Resembles the System in Bone Cells
Reidar Wallin
1   From the Department of Internal Medicine, Sections of Rheumatology and University School of Medicine, Winston-Salem, North Carolina, USA
,
Dean Cain
1   From the Department of Internal Medicine, Sections of Rheumatology and University School of Medicine, Winston-Salem, North Carolina, USA
,
David C. Sane
2   From the Department of Internal Medicine, Sections of, Cardiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
› Author AffiliationsThis work was supported by a grant from the North Carolina Biotechnology Center (Grant # 9805-ARG-0004).
Further Information

Publication History

Received 24 May 1999

Accepted after resubmission 04 August 1999

Publication Date:
10 December 2017 (online)

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Summary

Matrix GLA protein (MGP) is an inhibitor of calcification in the arterial wall and its activity is dependent upon vitamin K-dependent γ-carboxylation. This modification is carried out by a warfarin sensitive enzyme system that converts specific Glu residues to γ-carboxyglutamic acid (GLA) residues. Recent studies have demonstrated that the γ-carboxylation system in the arterial wall, in contrast to that in the liver, is unable to use vitamin K as an antidote to warfarin.

By use of immunohistochemistry we demonstrate that MGP is expressed in the arterial wall and immunocytochemistry localized the MGP precursors to the endoplasmic reticulum in vascular smooth muscle cells. Resting smooth vascular muscle cells in the aortic wall and proliferating cells from explants of the aorta have all the enzymes needed for γ-carboxylation of MGP. However, when compared to the liver system, expression of the enzymes of the γ-carboxylation system in vascular smooth muscle cells is different. Of particular interest is the finding that the specific activity of the warfarin sensitive enzyme vitamin K epoxide reductase is 3-fold higher in vascular smooth muscle cells than in liver. DT-diaphorase, which catalyses the antidotal pathway for vitamin K reduction in liver, is 100-fold less active in resting vascular smooth muscle cells than in liver. Data obtained from an in vitro γ-carboxylation system suggest that the antidotal pathway catalyzed by DT-diaphorase in the vessel wall is unable to provide the carboxylase with enough reduced vitamin K to trigger γ-carboxylation of MGP. This finding provides an explanation to the inability of vitamin K to work as an antidote to warfarin intoxication of the arterial wall. Therefore the vitamin K dependent γ-carboxylation system in the arterial wall share a common feature with the system in bone cells by being unable to utilize vitamin K as an antidote.

Keywords

Matrix GLA protein - vitamin K - arterial calcification - warfarin
 

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