Vascular calcification in patients with type 2 diabetes: the involvement of matrix Gla protein

Abstract

Background: Matrix Gla protein (MGP) is an important inhibitor of calcification. The objective of the present study of patients with type 2 diabetes and normal or slightly altered kidney function was to evaluate levels of inactive, dephospho-uncarboxylated MGP(dp-ucMGP) and total uncarboxylated MGP(t-ucMGP) and assess their links with biological and clinical parameters (including peripheral vascular calcification).

Methods: The DIACART study is a cross-sectional cohort study of 198 patients with type 2 diabetes and normal or slightly altered kidney function. Matrix Gla protein levels were measured with an ELISA and all patients underwent multislice spiral computed tomography scans to score below-knee arterial calcification.

Results: In the study population as a whole, the mean dp-ucMGP and t-ucMGP levels were 627 ± 451 pM and 4868 ± 1613 nM, respectively. Glomerular filtration rate, age and current vitamin K antagonist use were independently associated with dp-ucMGP levels. When the study population was divided according to the median peripheral arterial calcification score, patients with the higher score displayed significantly lower t-ucMGP and significantly higher dp-ucMGP levels. Furthermore, plasma dp-ucMGP was positively associated with the peripheral arterial calcification score (independently of age, gender, previous cardiovascular disease and t-ucMGP levels).

Conclusions: High dp-ucMGP levels were independently associated with below-knee arterial calcification score in patients with type 2 diabetes and normal or slightly altered kidney function. The reversibility of the elevation of dp-ucMGP levels and the latter's relationship with clinical events merit further investigation.

Figure 1

The different forms of the matrix Gla protein (MGP). legend: MGP needs two posttranslational modifications for maturation: glutamate carboxylation and serine phosphorylation. Both modifications are only partially accomplished. Besides the non-modified form (dp-ucMGP) also partially modified species (dp-cMGP and p-ucMGP) and the fully maturated form p-cMGP are present in the circulation. In this paper we have tested dp-ucMGP and total ucMGP (t-ucMGP) (which consists of the sum of dp-ucMGP and p-ucMGP). Since the plasma concentration of p-ucMGP is about 10 thousand fold higher than that of dp-ucMGP, the t-ucMGP assay virtually measures p-ucMGP.