Uncarboxylated matrix Gla protein (ucMGP) is associated with coronary artery calcification in haemodialysis patients
Ellen C. M. Cranenburg1,*; Vincent M. Brandenburg2,*; Cees Vermeer1; Melanie Stenger2; Georg Mühlenbruch3; Andreas H. Mahnken3; Ulrich Gladziwa4; Markus Ketteler2; Leon J. Schurgers1
1VitaK and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands; 2Department of Nephrology and Clinical Immunology, RWTH University Hospital Aachen, Germany; 3Department of Diagnostic Radiology, RWTH University Hospital Aachen, Germany; 4Department of Internal Medicine, University of Witten/Herdecke, Germany
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.
Gla-domain proteins, vitamin K, matrix Gla protein, Dialysis, calcification