The matrix-gla protein awakening may lead to the demise of vascular calcification

Matrix-gla-protein (MGP) is mainly secreted by chondrocytes and smooth vascular muscle cells. This potent inhibitor of vascular calcification need to undergo 2 post-transcriptional steps to be fully active: one phosphorylation of 3 serine residues (on 5) and a carboxylation of 5 glutamate residues (on 9). Like other "Gla" proteins, this carboxylation is vitamin K dependant. Several forms of MGP thus circulate in the plasma, some of them being totally inactive (the unphosphorylated and uncarboxylated MGP), some others being partially or fully active, according to the number of phosphorylated or carboxylated sites. A theoretical link exists between MGP, vitamin K, vascular calcifications and cardiovascular diseases. This link is even more evident in patients suffering from chronic kidney diseases (CKD), and notably hemodialysis patients. If this link has been demonstrated in different experimental studies, clinical studies are mainly observational and their results must be interpreted accordingly. MGP concentrations are definitely not yet a surrogate to estimate the levels of vascular calcification, but could allow the monitoring of vitamin K treatment. Modulation of MGP concentrations may reduce vascular calcification in hemodialyzed patients, if the large ongoing trials show an efficiency of this treatment. In this review, we will summarize the role of MGP in the vascular calcifications process, describe the problems linked to the analytical determination of MGP in plasma and finally describe the different clinical studies on MGP and vascular calcifications in the general population and in CKD patients. (C) 2015 Association Societe de nephrologie. Published by Elsevier Masson SAS. All rights reserved.