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Thromb Haemost 2009; 101(02): 359-366
DOI: 10.1160/TH08-04-0241
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Uncarboxylated matrix Gla protein (ucMGP) is associated with coronary artery calcification in haemodialysis patients

Ellen C. M. Cranenburg   *
1   VitaK and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
,
Vincent M. Brandenburg   *
2   Department of Nephrology and Clinical Immunology, RWTH University Hospital Aachen, Germany
,
Cees Vermeer
1   VitaK and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
,
Melanie Stenger
2   Department of Nephrology and Clinical Immunology, RWTH University Hospital Aachen, Germany
,
Georg Mühlenbruch
3   Department of Diagnostic Radiology, RWTH University Hospital Aachen, Germany
,
Andreas H. Mahnken
3   Department of Diagnostic Radiology, RWTH University Hospital Aachen, Germany
,
Ulrich Gladziwa
4   Department of Internal Medicine, University of Witten/Herdecke, Germany
,
Markus Ketteler
2   Department of Nephrology and Clinical Immunology, RWTH University Hospital Aachen, Germany
,
Leon J. Schurgers
1   VitaK and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
› Author AffiliationsFinancial support: This work was supported by a grant from GENZYME.
Further Information

Publication History

Received: 18 April 2008

Accepted after major revision: 11 January 2008

Publication Date:
23 November 2017 (online)

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Summary

Matrix γ-carboxyglutamate (Gla) protein (MGP) is a potent local inhibitor of cardiovascular calcification and accumulates at areas of calcification in its uncarboxylated form (ucMGP). We previously found significantly lower circulating ucMGP levels in patients with a high vascular calcification burden. Here we report on the potential of circulating ucMGP to serve as a biomarker for vascular calcification in haemodialysis (HD) patients. Circulating ucMGP levels were measured with an ELISA-based assay in 40 HD patients who underwent multi-slice computed tomography (MSCT) scanning to quantify the extent of coronary artery calcification (CAC). The mean ucMGP level in HD patients (193 ± 65 nM) was significantly lower as compared to apparently healthy subjects of the same age (441 ± 97 nM; p < 0.001) and patients with rheumatoid arthritis (RA) without CAC (560 ± 140 nM; p < 0.001). Additionally, ucMGP levels correlated inversely with CAC scores (r = –0.41; p = 0.009), and this correlation persisted after adjustment for age, dialysis vintage and high-sensitivity C-reactive protein (hs-CRP). Since circulating ucMGP levels are significantly and inversely correlated with the extent of CAC in HD patients, ucMGP may become a tool for identifying HD patients with a high probability of cardiovascular calcification.

Keywords

Calcification - dialysis - Gla-domain proteins - matrix Gla protein - vitamin K

* The first two authors have contributed equally to this work.


 

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