The Circulating Inactive Form of Matrix Gla Protein (ucMGP) as a Biomarker for Cardiovascular Calcification

• Published in: Journal of vascular research Vol. 45; no. 5; pp. 427 - 436
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2008; S. Karger AG
• Subjects: Adult; Angioplasty; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biomarkers - blood; Blood and lymphatic vessels; Calcinosis - metabolism; Calciphylaxis - metabolism; Calcium-Binding Proteins - blood; Cardiology. Vascular system; Coronary Artery Disease - metabolism; Coronary Artery Disease - surgery; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix Proteins - blood; Female; Fundamental and applied biological sciences. Psychology; Germany; Humans; Male; Matrix Gla Protein; Medical sciences; Middle Aged; Netherlands; Predictive Value of Tests; Reference Values; Renal Dialysis; Renal Insufficiency - metabolism; Renal Insufficiency - therapy; Reproducibility of Results; Research Paper; Vertebrates: cardiovascular system; Netherlands; Germany; Calcification; Extracellular matrix; Matrix Gla protein; Arteries; Atherosclerosis; Vitamin K; Matrix Gla protein, Vitamin K; Biological marker; Cardiovascular disease; Artery; Protein; Vascular disease; Vertebrata; Mammalia; Blood vessel; Circulatory system
• ISSN: 1018-1172; 1423-0135
• DOI: 10.1159/000124863

Objective: Matrix γ-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. Methods and Results: 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. Conclusion: 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.