Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species

Ellen C. M. Cranenburg; Ralf Koos; Leon J. Schurgers; Elke J. Magdeleyns; Thea H. M. Schoonbrood; Robert B. Landewé; Vincent M. Brandenburg; Otto Bekers; Cees Vermeer

doi:10.1160/TH09-11-0786

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 104(04): 811-822
DOI: 10.1160/TH09-11-0786

Cardiovascular Biology and Cell Signalling

Schattauer GmbH

Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species

Ellen C. M. Cranenburg

¹VitaK and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

,

Ralf Koos

²Department of Cardiology, RWTH University Hospital Aachen, Aachen, Germany

,

Leon J. Schurgers

¹VitaK and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

,

Elke J. Magdeleyns

¹VitaK and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

,

Thea H. M. Schoonbrood

³Department of Rheumatology, University Hospital Maastricht, Maastricht, the Netherlands

,

Robert B. Landewé

³Department of Rheumatology, University Hospital Maastricht, Maastricht, the Netherlands

,

Vincent M. Brandenburg

²Department of Cardiology, RWTH University Hospital Aachen, Aachen, Germany

⁴Department of Nephrology and Clinical Immunology, RWTH University Hospital Aachen, Aachen, Germany

,

Otto Bekers

⁵Department of Clinical Chemistry, University Hospital Maastricht, Maastricht, The Netherlands

,

Cees Vermeer

¹VitaK and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

› Author Affiliations

Abstract

Summary

Matrix γ-carboxyglutamate (Gla) protein (MGP) is an important local inhibitor of vascular calcification, which can undergo two post-translational modifications: vitamin K-dependent γ-glutamate carboxylation and serine phosphorylation. While carboxylation is thought to have effects upon binding of calcium-ions, phosphorylation is supposed to affect the cellular release of MGP. Since both modifications can be exerted incompletely, various MGP species can be detected in the circulation. MGP levels were measured with two commercially available competitive and two novel sandwich assays in healthy controls, in patients with rheumatic disease, aortic valve disease, and end-stage renal disease, as well as in volunteers after vitamin K supplementation (VKS) and treatment with vitamin K antagonists (VKA). Major differences were found between the MGP assays, including significantly different behaviour with regard to vascular disease and the response to VKA and VKS. The dual-antibody assay measuring non-phosphorylated, non-carboxylated MGP (dp-ucMGP) was particularly sensitive for these changes and would be suited to assess the vascular vitamin K status. We conclude that the different assays for particular circulating MGP species allows the assessment of various aspects of the MGP system.

Keywords

Calcification - cardiovascular disease - Gla-domain proteins - matrix Gla protein - vitamin K

Full Text

References

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