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

Ellen C. M. Cranenburg; Vincent M. Brandenburg; Cees Vermeer; Melanie Stenger; Georg Mühlenbruch; Andreas H. Mahnken; Ulrich Gladziwa; Markus Ketteler; Leon J. Schurgers

doi:10.1160/TH08-04-0241

Thrombosis and Haemostasis, Inhaltsverzeichnis

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^*

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

,

Vincent M. Brandenburg^*

²Department of Nephrology and Clinical Immunology, RWTH University Hospital Aachen, Germany

,

Cees Vermeer

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

,

Melanie Stenger

²Department of Nephrology and Clinical Immunology, RWTH University Hospital Aachen, Germany

,

Georg Mühlenbruch

³Department of Diagnostic Radiology, RWTH University Hospital Aachen, Germany

,

Andreas H. Mahnken

³Department of Diagnostic Radiology, RWTH University Hospital Aachen, Germany

,

Ulrich Gladziwa

⁴Department of Internal Medicine, University of Witten/Herdecke, Germany

,

Markus Ketteler

²Department of Nephrology and Clinical Immunology, RWTH University Hospital Aachen, Germany

,

Leon J. Schurgers

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

› Institutsangaben

Abstract

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

Volltext

Referenzen

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