Cranenburg Ellen C M, Vermeer Cees, Koos Ralf, Boumans Marie-Louise, Hackeng Tilman M, Bouwman Freek G, Kwaijtaal Martijn, Brandenburg Vincent M, Ketteler Markus, Schurgers Leon J
VitaK, Maastricht University, Maastricht, The Netherlands.
J Vasc Res. 2008;45(5):427-36. doi: 10.1159/000124863. Epub 2008 Apr 10.
Matrix gamma-carboxyglutamate (Gla) protein (MGP) is a vitamin K-dependent protein and a strong inhibitor of vascular calcification. Vitamin K deficiency leads to inactive uncarboxylated MGP (ucMGP), which accumulates at sites of arterial calcification. We hypothesized that as a result of ucMGP deposition around arterial calcification, the circulating fraction of ucMGP is decreased. Here we report on the development of an ucMGP assay and the potential diagnostic utility of monitoring serum ucMGP levels.
An ELISA-based assay was developed with which circulating ucMGP can be determined. Serum ucMGP levels were measured in healthy subjects (n = 165) and in four patient populations; patients who underwent angioplasty (n = 30), patients with aortic stenosis (n = 25), hemodialysis patients (n = 52), and calciphylaxis patients (n = 10). All four patient populations had significantly lower ucMGP levels. In angioplasty patients and in those with aortic stenosis, some overlap was observed with the control population. However, in the hemodialysis and calciphylaxis populations, virtually all subjects had ucMGP levels below the normal adult range.
Serum ucMGP may be used as a biomarker to identify those at risk for developing vascular calcification. This assay may become an important tool in the diagnosis of cardiovascular calcification.
基质γ-羧基谷氨酸（Gla）蛋白（MGP）是一种维生素K依赖蛋白，也是血管钙化的强效抑制剂。维生素K缺乏会导致无活性的未羧化MGP（ucMGP），其在动脉钙化部位蓄积。我们推测，由于ucMGP在动脉钙化周围沉积，其循环部分会减少。在此，我们报告ucMGP检测方法的开发以及监测血清ucMGP水平的潜在诊断效用。
开发了一种基于酶联免疫吸附测定（ELISA）的方法，可用于测定循环中的ucMGP。对健康受试者（n = 165）和四类患者群体的血清ucMGP水平进行了测量；接受血管成形术的患者（n = 30）、主动脉瓣狭窄患者（n = 25）、血液透析患者（n = 52）和钙化防御患者（n = 10）。所有四类患者群体的ucMGP水平均显著降低。在血管成形术患者和主动脉瓣狭窄患者中，观察到与对照组有一定重叠。然而，在血液透析和钙化防御人群中，几乎所有受试者的ucMGP水平均低于正常成人范围。
血清ucMGP可用作生物标志物，以识别有发生血管钙化风险的人群。该检测方法可能成为心血管钙化诊断的重要工具。
