Article

Matrix Gla-protein: the calcification inhibitor in need of vitamin K.

VitaK, Maastricht University, Universiteitssingel 50, Maastricht, The Netherlands.
Thrombosis and Haemostasis (Impact Factor: 5.76). 11/2008; 100(4):593-603.
Source: PubMed

ABSTRACT Among the proteins involved in vascular calcium metabolism, the vitamin K-dependent matrix Gla-protein (MGP) plays a dominant role. Although on a molecular level its mechanism of action is not completely understood, it is generally accepted that MGP is a potent inhibitor of arterial calcification. Its pivotal importance for vascular health is demonstrated by the fact that there seems to be no effective alternative mechanism for calcification inhibition in the vasculature. An optimal vitamin K intake is therefore important to maintain the risk and rate of calcification as low as possible. With the aid of conformation-specific antibodies MGP species in both tissue and the circulation have been detected in the healthy population, and significant differences were found in patients with cardiovascular disease (CVD). Using ELISA-based assays, uncarboxylated MGP (ucMGP) was demonstrated to be a promising biomarker for cardiovascular calcification detection. These assays may have potential value for identifying patients as well as apparently healthy subjects at high risk for CVD and/or cardiovascular calcification and for monitoring the treatment of CVD and vascular calcification.

1 Bookmark
 · 
148 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BMP-induced bone formation was evaluated in mice fed a Soy, Can, or H2-Soy diet.•Ectopic bone formation was greater in the Can and H2-Soy groups.•Altered levels of VK2 and VK-dependent protein(s) might affect the bone formation.
    Toxicology Reports 11/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Calcium oxalate (CaOx) kidney stones are formed attached to Randall's plaques (RPs) or Randall's plugs. Mechanisms involved in the formation and growth are poorly understood. It is our hypothesis that stone formation is a form of pathological biomineralization or ectopic calcification. Pathological calcification and plaque formation in the body is triggered by reactive oxygen species (ROS) and the development of oxidative stress (OS). This review explores clinical and experimental data in support of ROS involvement in the formation of CaOx kidney stones. Under normal conditions the production of ROS is tightly controlled, increasing when and where needed. Results of clinical and experimental studies show that renal epithelial exposure to high oxalate and crystals of CaOx/calcium phosphate (CaP) generates excess ROS, causing injury and inflammation. Major markers of OS and inflammation are detectable in urine of stone patients as well as rats with experimentally induced CaOx nephrolithiasis. Antioxidant treatments reduce crystal and oxalate induced injury in tissue culture and animal models. Significantly lower serum levels of antioxidants, alpha-carotene, beta-carotene and beta-cryptoxanthine have been found in individuals with a history of kidney stones. A diet rich in antioxidants has been shown to reduce stone episodes. ROS regulate crystal formation, growth and retention through the timely production of crystallization modulators. In the presence of abnormal calcium, citrate, oxalate, and/or phosphate, however, there is an overproduction of ROS and a decrease in the antioxidant capacity resulting in OS, renal injury and inflammation. Cellular degradation products in the urine promote crystallization in the tubular lumen at a faster rate thus blocking the tubule and plugging the tubular openings at the papillary tips forming Randall's plugs. Renal epithelial cells lining the loops of Henle/collecting ducts may become osteogenic, producing membrane vesicles at the basal side. In addition endothelial cells lining the blood vessels may also become osteogenic producing membrane vesicles. Calcification of the vesicles gives rise to RPs. The growth of the RP's is sustained by mineralization of collagen laid down as result of inflammation and fibrosis.
    Translational andrology and urology. 09/2014; 3(3):256-276.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: The main objective was to assess the interplay between circulating matrix Gla protein (MGP) - marker for vascular calcification, matrix metalloproteinase-9 (MMP-9) - marker for extracellular matrix remodeling and nitrotyrosine (NT) - marker for oxidative stress in patients with varicose veins (VV). Moreover, we wanted to investigate the behavior of these parameters before and after a stressful event (surgical removal of VV from lower limbs) and to find out if there is a contribution of MGP originating from superficial veins of the lower limb to the total pool of circulating MGP. Material and method: The pilot cohort study was accomplished on patients with VV (n=29) before and after a stressful event (surgical removal of VV from inferior limbs) and a group of age-gender matched apparently healthy volunteers (n=29). Plasma levels of tMGP, MMP-9 and NT were assayed with commercially available immunoassay kits. Results: Differences between patients with VV and age-sex matched healthy subjects were reflected only by higher levels of MMP-9 [82 (19-159) ng/mL versus 36 (2-108) ng/mL, p<0.05]; and not by circulating tMGP or NT levels. When patients before removal of VV were compared to patients after surgery, only tMGP was found significantly decreased [65 (32-97) μg/L versus 40 (17-95) μg/L, p<0.05]. We also found a correlation between tMGP and MMP-9 in patients with VV (r = 0.37, p<0.05). We did not find any correlation of NT with tMGP or MMP-9 and no significant differences in plasma NT levels in any pairwise comparisons. Conclusion: Higher circulating levels of MMP-9 could differentiate between healthy individuals and patients with chronic venous insufficiency. Consequently, oxidative stress assessed by NT did not affect circulating levels of tMGP or MMP-9 after surgical removal of VV. The constitutive decrease in plasma level of tMGP could be considered the contribution of MGP from superficial veins of the inferior limb to the total pool of circulating MGP
    HVM Bioflux. 02/2015;

Full-text

Download
106 Downloads
Available from
Jun 2, 2014