The Role of Matrix Gla Protein (MGP) in Vascular Calcification

Abstract

Matrix Gla protein (MGP) is a vitamin K-dependent protein, which is synthesized in bone and many other mesenchymal cells, which is also highly expressed by vascular smooth muscle cells (VSMCs) and chondrocytes. Numerous studies have confirmed that MGP acts as a calcification-inhibitor although the mechanism of action is still not fully understood. The modulation of tissue calcification by MGP is potentially regulated in several ways including direct inhibition of calcium-phosphate precipitation, the formation of matrix vesicles (MVs), the formation of apoptotic bodies (ABs), and trans-differentiation of VSMCs. MGP occurs as four species, i.e. fully carboxylated (cMGP), under-carboxylated, i.e. poorly carboxylated (ucMGP), phosphorylated (pMGP), and non-phosphorylated (desphospho, dpMGP). ELISA methods are currently available that can detect the different species of MGP. The expression of the MGP gene can be regulated via various mechanisms that have the potential to become genomic biomarkers for the prediction of vascular calcification (VC) progression. VC is an established risk factor for cardiovascular disease and is particularly prevalent in those with chronic kidney disease (CKD). The specific action of MGP is not yet clearly understood but could be involved with the functional inhibition of BMP-2 and BMP-4, by blocking calcium crystal deposition and shielding the nidus from calcification.

Relationship of matrix Gla protein and vitamin K with vascular calcification in hemodialysis patients

“…MGP, osteopontin, osteoprotegerin, fetuin A, klotho, vitamin K, and magnesium) in CKD may cause development of vascular calcification [16,25]. The precise function of MGP has not been elucidated, but may include calcium crystal growth, blockage of bone morphogenetic protein (BMP)-2 and BMP-4 functions, and inhibition of vascular calcification [16,26]. Low levels of vascular calcification are present in predialysis CKD, and vascular calcification significantly increases in patients on dialysis [25].…”

New Insights on Vitamin K Metabolism in Senegalese sole (Solea senegalensis) Based on Ontogenetic and Tissue-Specific Vitamin K Epoxide Reductase Molecular Data

“…In this regard, although a one day fasting increases weaning success in Senegalese sole larvae, it also increases the incidence of skeletal deformities up to 88%, particularly at the neural arch, pleural and caudal vertebrae [88]. Here, a short fasting period of two days did not alter the expression levels of ssvkorc1, but it increased the expression of ssvkorc1l1, suggesting that extra-hepatic (but not the hepatic) γ-carboxylation of VKDPs, related to arterial uncalcification (Mgp; [89]) and bone mineralization (Bgp; [90]), may be compromised. Consequently, increased expression of both sskvors after three days re-feeding with a VK1 (1250VK) rich diet might be in line with: (i) increased dietary VK1 supplementation in the case of ssvkorc1, and a still unrecovered situation on extra-hepatic VK status regarding ssvkorc1l1 gene expression, even when fed a VK1 rich diet; or (ii) the reported period of metabolic adjustments directed toward the physiological condition restoration after a fasting period [91].…”

A guide to crystal‐related and nano‐ or microparticle‐related tissue responses

“…Within the urinary tract, uromodulin is immunologically inert and masks the pro‐inflammatory and cytotoxic potential of crystals, although once picked up by phagocytes, uromodulin itself can activate the NLRP3 inflammasome, for example, when tubular epithelial cell damage exposes uromodulin particles to resident or infiltrating mononuclear phagocytes in the kidney . Vascular deposits of calcium phosphate crystals cause vascular wall or heart valve calcifications that are a central element of numerous cardiovascular complications of diabetes and chronic kidney disease and often relate to a dysbalance of calcification inhibitors such as matrix Gla protein and fetuin‐A . These calcium phosphate deposits are usually devoid of any inflammatory response and rather mimic the process of ossification.…”