Abstract
BackgroundMatrix Gla protein (MGP) is known to act as a potent local inhibitor of vascular calcifications. However, in order to be active, MGP must be phosphorylated and carboxylated, with this last process being dependent on vitamin K. The present study focused on the inactive form of MGP (dephosphorylated and uncarboxylated: dp-ucMGP) in a population of hemodialyzed (HD) patients. Results found in subjects being treated or not with vitamin K antagonist (VKA) were compared and the relationship between dp-ucMGP levels and the vascular calcification score were assessed.MethodsOne hundred sixty prevalent HD patients were enrolled into this observational cohort study, including 23 who were receiving VKA treatment. The calcification score was determined (using the Kauppila method) and dp-ucMGP levels were measured using the automated iSYS method.Resultsdp-ucMGP levels were much higher in patients being treated with VKA and little overlap was found with those not being treated (5604 [3758; 7836] vs. 1939 [1419; 2841] pmol/L, p <0.0001). In multivariate analysis, treatment with VKA was the most important variable explaining variation in dp-ucMGP levels even when adjusting for all other significant variables. In the 137 untreated patients, dp-ucMGP levels were significantly (p < 0.05) associated both in the uni- and multivariate analysis with age, body mass index, plasma levels of albumin, C-reactive protein, and FGF-23, and the vascular calcification score.ConclusionWe confirmed that the concentration of dp-ucMGP was higher in HD patients being treated with VKA. We observed a significant correlation between dp-ucMGP concentration and the calcification score. Our data support the theoretical role of MGP in the development of vascular calcifications. We confirmed the potential role of the inactive form of MGP in assessing the vitamin K status of the HD patients.Trial registrationB707201215885
Highlights
Matrix Gla protein (MGP) is known to act as a potent local inhibitor of vascular calcifications
We showed for the first time that dialysis patients treated by vitamin K antagonist (VKA) have significantly higher dp-ucMGP concentrations than not treated dialysis patients
We confirmed the potential usefulness of MGP in the assessment of vascular calcifications, this finding has, to date, been the subject of debate in the literature
Summary
Matrix Gla protein (MGP) is known to act as a potent local inhibitor of vascular calcifications. In order to be fully active, MGP must first undergo two posttranslational processes: the phosphorylation of three serine residues ( the role of this phosphorylation process is still not well understood) and the carboxylation of five glutamate residues [5,6]. This explains why it is theoretically possible for several different isoforms of MGP to be measured in the plasma (a combination of carboxylated, uncarboxylated and phosphorylated, unphosphorylated MGP). Because γ-glutamyl carboxylation is highly dependent on availability of vitamin K [9], it is possible that the measurement of dp-ucMGP would reflect vitamin K status [7,10]
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