The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Cranenburg
Ellen C M
EC
VitaK, Maastricht University, Maastricht, The Netherlands.
Vermeer
Cees
C
Koos
Ralf
R
Boumans
Marie-Louise
ML
Hackeng
Tilman M
TM
Bouwman
Freek G
FG
Kwaijtaal
Martijn
M
Brandenburg
Vincent M
VM
Ketteler
Markus
M
Schurgers
Leon J
LJ
D000328:Adult; D017130:Angioplasty; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000378:metabolism*; D002115:Calciphylaxis / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000097:blood*; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000601:surgery; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011237:Predictive Value of Tests; D012016:Reference Values; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000378:metabolism* / Q000628:therapy; D015203:Reproducibility of Results; D000097568:Matrix Gla Protein
D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein