Cranenburg Ellen C M, Brandenburg Vincent M, Vermeer Cees, Stenger Melanie, Mühlenbruch Georg, Mahnken Andreas H, Gladziwa Ulrich, Ketteler Markus, Schurgers Leon J
Department of Biochemistry, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
Thromb Haemost. 2009 Feb;101(2):359-66.
Matrix gamma-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.
基质γ-羧基谷氨酸(Gla)蛋白(MGP)是一种强效的心血管钙化局部抑制剂,以未羧化形式(ucMGP)在钙化区域积聚。我们之前发现,血管钙化负担高的患者循环中ucMGP水平显著降低。在此,我们报告循环ucMGP作为血液透析(HD)患者血管钙化生物标志物的潜力。采用基于酶联免疫吸附测定(ELISA)的方法,对40例接受多层计算机断层扫描(MSCT)以量化冠状动脉钙化(CAC)程度的HD患者测定循环ucMGP水平。HD患者的平均ucMGP水平(193±65 nM)显著低于同龄健康受试者(441±97 nM;p<0.001)和无CAC的类风湿关节炎(RA)患者(560±140 nM;p<0.001)。此外,ucMGP水平与CAC评分呈负相关(r = -0.41;p = 0.009),在对年龄、透析时间和高敏C反应蛋白(hs-CRP)进行校正后,这种相关性仍然存在。由于HD患者循环ucMGP水平与CAC程度显著负相关,ucMGP可能成为识别心血管钙化可能性高的HD患者的一种工具。