Generic placeholder image

Current Medicinal Chemistry

Author(s): Geir Bjørklund*, Erik Svanberg, Maryam Dadar, David J. Card, Salvatore Chirumbolo, Dominic J. Harrington and Jan Aaseth

DOI: 10.2174/0929867325666180716104159

DownloadDownload PDF Flyer Cite As
The Role of Matrix Gla Protein (MGP) in Vascular Calcification

Page: [1647 - 1660] Pages: 14

  • * (Excluding Mailing and Handling)

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.

Keywords: Matrix gla protein, vascular calcification, cardiovascular diseases, vitamin K, MGP, VSMCs.

[1]
Mahmood, S.S.; Levy, D.; Vasan, R.S.; Wang, T.J. The Framingham Heart Study and the epidemiology of cardiovascular disease: a historical perspective. Lancet, 2014, 383(9921), 999-1008.
[http://dx.doi.org/10.1016/S0140-6736(13)61752-3] [PMID: 24084292]
[2]
Rennenberg, R.J.; Kessels, A.G.; Schurgers, L.J.; van Engelshoven, J.M.; de Leeuw, P.W.; Kroon, A.A. Vascular calcifications as a marker of increased cardiovascular risk: a meta-analysis. Vasc. Health Risk Manag., 2009, 5(1), 185-197.
[http://dx.doi.org/10.2147/VHRM.S4822] [PMID: 19436645]
[3]
Nitta, K.; Ogawa, T. Vascular calcification in end-stage renal disease patients in: Chronic Kidney Diseases-Recent Advances in Clinical and Basic Research; Nitta, K., Ed.; Karger Publishers, 2015, Vol. 185, pp. 156-167.
[http://dx.doi.org/10.1159/000380980]
[4]
Chen, N.X.; Moe, S.M. Pathophysiology of vascular calcification. Curr. Osteoporos. Rep., 2015, 13(6), 372-380.
[http://dx.doi.org/10.1007/s11914-015-0293-9] [PMID: 26409849]
[5]
Evrard, S.; Delanaye, P.; Kamel, S.; Cristol, J-P.; Cavalier, E.; Arnaud, J.; Zaoui, P.; Carlier, M.; Laville, M.; Fouque, D. Vascular calcification: from pathophysiology to biomarkers. Clin. Chim. Acta, 2015, 438, 401-414.
[http://dx.doi.org/10.1016/j.cca.2014.08.034] [PMID: 25236333]
[6]
Pham, P.H.; Rao, D.S.; Vasunilashorn, F.; Fishbein, M.C.; Goldin, J.G. Computed tomography calcium quantification as a measure of atherosclerotic plaque morphology and stability. Invest. Radiol., 2006, 41(9), 674-680.
[http://dx.doi.org/10.1097/01.rli.0000233325.42572.08] [PMID: 16896302]
[7]
Liu, W.; Zhang, Y.; Yu, C-M.; Ji, Q-W.; Cai, M.; Zhao, Y-X.; Zhou, Y-J. Current understanding of coronary artery calcification. J. Geriatr. Cardiol., 2015, 12(6), 668-675.
[http://dx.doi.org/10.11909/j.issn.1671-5411.2015.06.012] [PMID: 26788045]
[8]
Price, P.A.; Fraser, J.D.; Metz-Virca, G. Molecular cloning of matrix Gla protein: implications for substrate recognition by the vitamin K-dependent gamma-carboxylase. Proc. Natl. Acad. Sci. USA, 1987, 84(23), 8335-8339.
[http://dx.doi.org/10.1073/pnas.84.23.8335] [PMID: 3317405]
[9]
Schurgers, L.J.; Cranenburg, E.C.; Vermeer, C. Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb. Haemost., 2008, 100(4), 593-603.
[PMID: 18841280]
[10]
Viegas, C.S.; Rafael, M.S.; Enriquez, J.L.; Teixeira, A.; Vitorino, R.; Luís, I.M.; Costa, R.M.; Santos, S.; Cavaco, S.; Neves, J.; Macedo, A.L.; Willems, B.A.; Vermeer, C.; Simes, D.C. Gla-rich protein acts as a calcification inhibitor in the human cardiovascular system. Arterioscler. Thromb. Vasc. Biol., 2015, 35(2), 399-408.
[http://dx.doi.org/10.1161/ATVBAHA.114.304823] [PMID: 25538207]
[11]
Mizobuchi, M.; Towler, D.; Slatopolsky, E. Vascular calcification: the killer of patients with chronic kidney disease. J. Am. Soc. Nephrol., 2009, 20(7), 1453-1464.
[http://dx.doi.org/10.1681/ASN.2008070692] [PMID: 19478096]
[12]
Horn, P.; Erkilet, G.; Veulemans, V.; Kröpil, P.; Schurgers, L.; Zeus, T.; Heiss, C.; Kelm, M.; Westenfeld, R. Microparticle-induced coagulation relates to coronary artery atherosclerosis in severe aortic valve stenosis. PLoS One, 2016, 11(3), e0151499
[http://dx.doi.org/10.1371/journal.pone.0151499] [PMID: 27010400]
[13]
Jarray, R.; Pavoni, S.; Borriello, L.; Allain, B.; Lopez, N.; Bianco, S.; Liu, W-Q.; Biard, D.; Demange, L.; Hermine, O.; Garbay, C.; Raynaud, F.; Lepelletier, Y. Disruption of phactr-1 pathway triggers pro-inflammatory and pro-atherogenic factors: New insights in atherosclerosis development. Biochimie, 2015, 118, 151-161.
[http://dx.doi.org/10.1016/j.biochi.2015.09.008] [PMID: 26362351]
[14]
Qiu, C.; Zheng, H.; Tao, H.; Yu, W.; Jiang, X.; Li, A.; Jin, H.; Lv, A.; Li, H. Vitamin K2 inhibits rat vascular smooth muscle cell calcification by restoring the Gas6/Axl/Akt anti-apoptotic pathway. Mol. Cell. Biochem., 2017, 433(1-2), 149-159.
[http://dx.doi.org/10.1007/s11010-017-3023-z] [PMID: 28386842]
[15]
Reyes García, R.; Rozas Moreno, P.; Muñoz-Torres, M. Osteocalcin and atherosclerosis: a complex relationship. Diabetes Res. Clin. Pract., 2011, 92(3), 405-406.
[http://dx.doi.org/10.1016/j.diabres.2010.08.019] [PMID: 20832889]
[16]
Schwanekamp, J.A.; Lorts, A.; Vagnozzi, R.J.; Vanhoutte, D.; Molkentin, J.D. Deletion of periostin protects against atherosclerosis in mice by altering inflammation and extracellular matrix remodeling. Arterioscler. Thromb. Vasc. Biol., 2016, 36(1), 60-68.
[http://dx.doi.org/10.1161/ATVBAHA.115.306397] [PMID: 26564821]
[17]
Cassidy-Bushrow, A.E.; Bielak, L.F.; Levin, A.M.; Sheedy, P.F., II; Turner, S.T.; Boerwinkle, E.; Lin, X.; Kardia, S.L.; Peyser, P.A. Matrix gla protein gene polymorphism is associated with increased coronary artery calcification progression. Arterioscler. Thromb. Vasc. Biol., 2013, 33(3), 645-651.
[http://dx.doi.org/10.1161/ATVBAHA.112.300491] [PMID: 23307874]
[18]
Herrmann, S-M.; Whatling, C.; Brand, E.; Nicaud, V.; Gariepy, J.; Simon, A.; Evans, A.; Ruidavets, J-B.; Arveiler, D.; Luc, G.; Tiret, L.; Henney, A.; Cambien, F. Polymorphisms of the human matrix gla protein (MGP) gene, vascular calcification, and myocardial infarction. Arterioscler. Thromb. Vasc. Biol., 2000, 20(11), 2386-2393.
[http://dx.doi.org/10.1161/01.ATV.20.11.2386] [PMID: 11073842]
[19]
Moe, S.M.; Chen, N.X. Mechanisms of vascular calcification in chronic kidney disease. J. Am. Soc. Nephrol., 2008, 19(2), 213-216.
[http://dx.doi.org/10.1681/ASN.2007080854] [PMID: 18094365]
[20]
Goodman, W.G.; London, G.; Amann, K.; Block, G.A.; Giachelli, C.; Hruska, K.A.; Ketteler, M.; Levin, A.; Massy, Z.; McCarron, D.A.; Raggi, P.; Shanahan, C.M.; Yorioka, N. Vascular calcification in chronic kidney disease. Am. J. Kidney Dis., 2004, 43(3), 572-579.
[http://dx.doi.org/10.1053/j.ajkd.2003.12.005] [PMID: 14981617]
[21]
Jono, S.; Shioi, A.; Ikari, Y.; Nishizawa, Y. Vascular calcification in chronic kidney disease. J. Bone Miner. Metab., 2006, 24(2), 176-181.
[http://dx.doi.org/10.1007/s00774-005-0668-6] [PMID: 16502129]
[22]
Cheung, C-L.; Sahni, S.; Cheung, B.M.; Sing, C-W.; Wong, I.C. Vitamin K intake and mortality in people with chronic kidney disease from NHANES III. Clin. Nutr., 2015, 34(2), 235-240.
[http://dx.doi.org/10.1016/j.clnu.2014.03.011] [PMID: 24745600]
[23]
Shearer, M.J.; Newman, P. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J. Lipid Res., 2014, 55(3), 345-362.
[http://dx.doi.org/10.1194/jlr.R045559] [PMID: 24489112]
[24]
Card, D.J.; Gorska, R.; Cutler, J.; Harrington, D.J. Vitamin K metabolism: current knowledge and future research. Mol. Nutr. Food Res., 2014, 58(8), 1590-1600.
[http://dx.doi.org/10.1002/mnfr.201300683] [PMID: 24376012]
[25]
Harrington, D.J.; Soper, R.; Edwards, C.; Savidge, G.F.; Hodges, S.J.; Shearer, M.J. Determination of the urinary aglycone metabolites of vitamin K by HPLC with redox-mode electrochemical detection. J. Lipid Res., 2005, 46(5), 1053-1060.
[http://dx.doi.org/10.1194/jlr.D400033-JLR200] [PMID: 15722567]
[26]
Card, D.J.; Shearer, M.J.; Schurgers, L.J.; Harrington, D.J. The external quality assurance of phylloquinone (vitamin K(1)) analysis in human serum. Biomed. Chromatogr., 2009, 23(12), 1276-1282.
[http://dx.doi.org/10.1002/bmc.1250] [PMID: 19488978]
[27]
Fraser, J.D.; Otawara, Y.; Price, P.A. 1,25-Dihydroxyvitamin D3 stimulates the synthesis of matrix gamma-carboxyglutamic acid protein by osteosarcoma cells. Mutually exclusive expression of vitamin K-dependent bone proteins by clonal osteoblastic cell lines. J. Biol. Chem., 1988, 263(2), 911-916.
[PMID: 3257212]
[28]
Cancela, M.L.; Ohresser, M.C.; Reia, J.P.; Viegas, C.S.; Williamson, M.K.; Price, P.A. Matrix Gla protein in Xenopus laevis: molecular cloning, tissue distribution, and evolutionary considerations. J. Bone Miner. Res., 2001, 16(9), 1611-1621.
[http://dx.doi.org/10.1359/jbmr.2001.16.9.1611] [PMID: 11550673]
[29]
Ahmad, S.; Jan, A.T.; Baig, M.H.; Lee, E.J.; Choi, I. Matrix gla protein: An extracellular matrix protein regulates myostatin expression in the muscle developmental program. Life Sci., 2017, 172, 55-63.
[http://dx.doi.org/10.1016/j.lfs.2016.12.011] [PMID: 28012893]
[30]
Cancela, L.; Hsieh, C.L.; Francke, U.; Price, P.A. Molecular structure, chromosome assignment, and promoter organization of the human matrix Gla protein gene. J. Biol. Chem., 1990, 265(25), 15040-15048.
[PMID: 2394711]
[31]
Kirfel, J.; Kelter, M.; Cancela, L.M.; Price, P.A.; Schüle, R. Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene. Proc. Natl. Acad. Sci. USA, 1997, 94(6), 2227-2232.
[http://dx.doi.org/10.1073/pnas.94.6.2227] [PMID: 9122176]
[32]
Kobayashi, N.; Kitazawa, R.; Maeda, S.; Schurgers, L.; Kitazawa, S. T-138C polymorphism of matrix gla protein promoter alters its expression but is not directly associated with atherosclerotic vascular calcification. Kobe J. Med. Sci., 2004, 50(3-4), 69-81.
[PMID: 15864013]
[33]
Doğan, G.E.; Demir, T.; Aksoy, H.; Sağlam, E.; Laloğlu, E.; Yildirim, A. Matrix-Gla Protein rs4236 [A/G] gene polymorphism and serum and GCF levels of MGP in patients with subgingival dental calculus. Arch. Oral Biol., 2016, 70, 125-129.
[http://dx.doi.org/10.1016/j.archoralbio.2016.06.014] [PMID: 27348051]
[34]
Price, P.A.; Williamson, M.K. Primary structure of bovine matrix Gla protein, a new vitamin K-dependent bone protein. J. Biol. Chem., 1985, 260(28), 14971-14975.
[PMID: 3877721]
[35]
Nigwekar, S.U.; Bloch, D.B.; Nazarian, R.M.; Vermeer, C.; Booth, S.L.; Xu, D.; Thadhani, R.I.; Malhotra, R. Vitamin K–dependent carboxylation of matrix Gla protein influences the risk of calciphylaxis. J. Am. Soc. Nephrol., 2017, 28(6), 1717-1722.
[http://dx.doi.org/10.1681/ASN.2016060651] [PMID: 28049648]
[36]
Roy, M.E.; Nishimoto, S.K. Matrix Gla protein binding to hydroxyapatite is dependent on the ionic environment: calcium enhances binding affinity but phosphate and magnesium decrease affinity. Bone, 2002, 31(2), 296-302.
[http://dx.doi.org/10.1016/S8756-3282(02)00821-9] [PMID: 12151082]
[37]
Schurgers, L.J.; Uitto, J.; Reutelingsperger, C.P. Vitamin K-dependent carboxylation of matrix Gla-protein: a crucial switch to control ectopic mineralization. Trends Mol. Med., 2013, 19(4), 217-226.
[http://dx.doi.org/10.1016/j.molmed.2012.12.008] [PMID: 23375872]
[38]
Murshed, M.; Schinke, T.; McKee, M.D.; Karsenty, G. Extracellular matrix mineralization is regulated locally; different roles of two gla-containing proteins. J. Cell Biol., 2004, 165(5), 625-630.
[http://dx.doi.org/10.1083/jcb.200402046] [PMID: 15184399]
[39]
Price, P.A.; Urist, M.R.; Otawara, Y. Matrix Gla protein, a new γ-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone. Biochem. Biophys. Res. Commun., 1983, 117(3), 765-771.
[http://dx.doi.org/10.1016/0006-291X(83)91663-7] [PMID: 6607731]
[40]
Shanahan, C.M.; Kapustin, A.N. Google Patents, 2015.
[41]
Price, P.A.; Nguyen, T.M.T.; Williamson, M.K. Biochemical characterization of the serum fetuin-mineral complex. J. Biol. Chem., 2003, 278(24), 22153-22160.
[http://dx.doi.org/10.1074/jbc.M300739200] [PMID: 12676928]
[42]
Wallin, R.; Cain, D.; Hutson, S.M.; Sane, D.C.; Loeser, R. Modulation of the binding of matrix Gla protein (MGP) to bone morphogenetic protein-2 (BMP-2). Thromb. Haemost., 2000, 84(6), 1039-1044.
[PMID: 11154111]
[43]
Zebboudj, A.F.; Imura, M.; Boström, K. Matrix GLA protein, a regulatory protein for bone morphogenetic protein-2. J. Biol. Chem., 2002, 277(6), 4388-4394.
[http://dx.doi.org/10.1074/jbc.M109683200] [PMID: 11741887]
[44]
Luo, G.; Ducy, P.; McKee, M.D.; Pinero, G.J.; Loyer, E.; Behringer, R.R.; Karsenty, G. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature, 1997, 386(6620), 78-81.
[http://dx.doi.org/10.1038/386078a0] [PMID: 9052783]
[45]
Wu, S-M.; Cheung, W-F.; Frazier, D.; Stafford, D.W. Cloning and expression of the cDNA for human gamma-glutamyl carboxylase. Science, 1991, 254(5038), 1634-1636.
[http://dx.doi.org/10.1126/science.1749935] [PMID: 1749935]
[46]
Bristol, J.A.; Ratcliffe, J.V.; Roth, D.A.; Jacobs, M.A.; Furie, B.C.; Furie, B. Biosynthesis of prothrombin: intracellular localization of the vitamin K-dependent carboxylase and the sites of gamma-carboxylation. Blood, 1996, 88(7), 2585-2593.
[http://dx.doi.org/10.1182/blood.V88.7.2585.bloodjournal8872585] [PMID: 8839851]
[47]
Card, D.J.; Shearer, M.J.; Schurgers, L.J.; Gomez, K.; Harrington, D.J. What’s in a name? The pharmacy of vitamin K. Br. J. Haematol., 2016, 174(6), 989-990.
[http://dx.doi.org/10.1111/bjh.13828] [PMID: 26492096]
[48]
Thijssen, H.H.; Drittij-Reijnders, M.J. Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone-4. Br. J. Nutr., 1994, 72(3), 415-425.
[http://dx.doi.org/10.1079/BJN19940043] [PMID: 7947656]
[49]
Suganthi, M.; Elango, K.P. Synthesis, characterization and serum albumin binding studies of vitamin K3 derivatives. J. Photochem. Photobiol. B, 2017, 166, 126-135.
[http://dx.doi.org/10.1016/j.jphotobiol.2016.11.016] [PMID: 27898366]
[50]
Conly, J.M.; Stein, K.; Worobetz, L.; Rutledge-Harding, S. The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K. Am. J. Gastroenterol., 1994, 89(6), 915-923.
[PMID: 8198105]
[51]
Walther, B.; Chollet, M. Menaquinones, bacteria, and foods: vitamin K2 in the diet in: Vitamin K2-vital for health and wellbeing; Gordeladze, J., Ed.; InTech, 2017.
[http://dx.doi.org/10.5772/63712]
[52]
Wajih, N.; Sane, D.C.; Hutson, S.M.; Wallin, R. The inhibitory effect of calumenin on the vitamin K-dependent γ-carboxylation system. Characterization of the system in normal and warfarin-resistant rats. J. Biol. Chem., 2004, 279(24), 25276-25283.
[http://dx.doi.org/10.1074/jbc.M401645200] [PMID: 15075329]
[53]
Ketteler, M.; Wanner, C.; Metzger, T.; Bongartz, P.; Westenfeld, R.; Gladziwa, U.; Schurgers, L.J.; Vermeer, C.; Jahnen-Dechent, W.; Floege, J. Deficiencies of calcium-regulatory proteins in dialysis patients: a novel concept of cardiovascular calcification in uremia. Kidney Int. Suppl., 2003, 63(84), S84-S87.
[http://dx.doi.org/10.1046/j.1523-1755.63.s84.21.x] [PMID: 12694317]
[54]
Shanahan, C.M.; Cary, N.R.; Metcalfe, J.C.; Weissberg, P.L. High expression of genes for calcification-regulating proteins in human atherosclerotic plaques. J. Clin. Invest., 1994, 93(6), 2393-2402.
[http://dx.doi.org/10.1172/JCI117246] [PMID: 8200973]
[55]
Stehbens, W.E. The significance of programmed cell death or apoptosis and matrix vesicles in atherogenesis. Cell. Mol. Biol., 2000, 46(1), 99-110.
[PMID: 10726976]
[56]
Reynolds, J.L.; Joannides, A.J.; Skepper, J.N.; McNair, R.; Schurgers, L.J.; Proudfoot, D.; Jahnen-Dechent, W.; Weissberg, P.L.; Shanahan, C.M. Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD. J. Am. Soc. Nephrol., 2004, 15(11), 2857-2867.
[http://dx.doi.org/10.1097/01.ASN.0000141960.01035.28] [PMID: 15504939]
[57]
Tabb, M.M.; Sun, A.; Zhou, C.; Grün, F.; Errandi, J.; Romero, K.; Pham, H.; Inoue, S.; Mallick, S.; Lin, M.; Forman, B.M.; Blumberg, B. Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. J. Biol. Chem., 2003, 278(45), 43919-43927.
[http://dx.doi.org/10.1074/jbc.M303136200] [PMID: 12920130]
[58]
Moe, S.M.; Reslerova, M.; Ketteler, M.; O’neill, K.; Duan, D.; Koczman, J.; Westenfeld, R.; Jahnen-Dechent, W.; Chen, N.X. Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD). Kidney Int., 2005, 67(6), 2295-2304.
[http://dx.doi.org/10.1111/j.1523-1755.2005.00333.x] [PMID: 15882271]
[59]
Yoshikawa, K.; Abe, H.; Tominaga, T.; Nakamura, M.; Kishi, S.; Matsuura, M.; Nagai, K.; Tsuchida, K.; Minakuchi, J.; Doi, T. Polymorphism in the human matrix Gla protein gene is associated with the progression of vascular calcification in maintenance hemodialysis patients. Clin. Exp. Nephrol., 2013, 17(6), 882-889.
[http://dx.doi.org/10.1007/s10157-013-0785-9] [PMID: 23504408]
[60]
Sheng, K.; Zhang, P.; Lin, W.; Cheng, J.; Li, J.; Chen, J. Association of Matrix Gla protein gene (rs1800801, rs1800802, rs4236) polymorphism with vascular calcification and atherosclerotic disease: a meta-analysis. Sci. Rep., 2017, 7(1), 8713.
[http://dx.doi.org/10.1038/s41598-017-09328-5] [PMID: 28821877]
[61]
Cranenburg, E.C.; Koos, R.; Schurgers, L.J.; Magdeleyns, E.J.; Schoonbrood, T.H.; Landewé, R.B.; Brandenburg, V.M.; Bekers, O.; Vermeer, C. Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species. Thromb. Haemost., 2010, 104(4), 811-822.
[http://dx.doi.org/10.1160/TH09-11-0786] [PMID: 20694284]
[62]
Holden, R.M.; Booth, S.L. Vascular calcification in chronic kidney disease: the role of vitamin K. Nat. Clin. Pract. Nephrol., 2007, 3(10), 522-523.
[http://dx.doi.org/10.1038/ncpneph0601] [PMID: 17768408]
[63]
Gast, G-C.M.; de Roos, N.M.; Sluijs, I.; Bots, M.L.; Beulens, J.W.; Geleijnse, J.M.; Witteman, J.C.; Grobbee, D.E.; Peeters, P.H.; van der Schouw, Y.T. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr. Metab. Cardiovasc. Dis., 2009, 19(7), 504-510.
[http://dx.doi.org/10.1016/j.numecd.2008.10.004] [PMID: 19179058]
[64]
Yagami, K.; Suh, J-Y.; Enomoto-Iwamoto, M.; Koyama, E.; Abrams, W.R.; Shapiro, I.M.; Pacifici, M.; Iwamoto, M. Matrix GLA protein is a developmental regulator of chondrocyte mineralization and, when constitutively expressed, blocks endochondral and intramembranous ossification in the limb. J. Cell Biol., 1999, 147(5), 1097-1108.
[http://dx.doi.org/10.1083/jcb.147.5.1097] [PMID: 10579728]
[65]
Wallin, R.; Schurgers, L.J.; Loeser, R.F. Biosynthesis of the vitamin K-dependent matrix Gla protein (MGP) in chondrocytes: a fetuin-MGP protein complex is assembled in vesicles shed from normal but not from osteoarthritic chondrocytes. Osteoarthritis Cartilage, 2010, 18(8), 1096-1103.
[http://dx.doi.org/10.1016/j.joca.2010.05.013] [PMID: 20510384]
[66]
Munroe, P.B.; Olgunturk, R.O.; Fryns, J-P.; Van Maldergem, L.; Ziereisen, F.; Yuksel, B.; Gardiner, R.M.; Chung, E. Mutations in the gene encoding the human matrix Gla protein cause Keutel syndrome. Nat. Genet., 1999, 21(1), 142-144.
[http://dx.doi.org/10.1038/5102] [PMID: 9916809]
[67]
Weaver, K.N.; El Hallek, M.; Hopkin, R.J.; Sund, K.L.; Henrickson, M.; Del Gaudio, D.; Yuksel, A.; Acar, G.O.; Bober, M.B.; Kim, J.; Boyadjiev, S.A. Keutel syndrome: report of two novel MGP mutations and discussion of clinical overlap with arylsulfatase E deficiency and relapsing polychondritis. Am. J. Med. Genet. A., 2014, 164A(4), 1062-1068.
[http://dx.doi.org/10.1002/ajmg.a.36390] [PMID: 24458983]
[68]
Hur, D.J.; Raymond, G.V.; Kahler, S.G.; Riegert-Johnson, D.L.; Cohen, B.A.; Boyadjiev, S.A. A novel MGP mutation in a consanguineous family: review of the clinical and molecular characteristics of Keutel syndrome. Am. J. Med. Genet. A., 2005, 135(1), 36-40.
[http://dx.doi.org/10.1002/ajmg.a.30680] [PMID: 15810001]
[69]
Sun, L.F.; Ju, Y.F.; Fu, G.J.; Wang, J.R.; Feng, Y.Z.; Chen, X. [Keutel syndrome with tracheal stenosis as the major symptom: case report and literature review]. Zhonghua Er Ke Za Zhi, 2013, 51(7), 527-530.
[PMID: 24267135]
[70]
Vermeer, C.; Drummen, N.E.; Knapen, M.H.; Zandbergen, F.J. Uncarboxylated Matrix Gla Protein as a Biomarker in Cardiovascular Disease: Applications for Research and for Routine Diagnostics in; Biomarkers in Cardiovascular Disease, 2015, pp. 267-283.
[http://dx.doi.org/10.1007/978-94-007-7678-4_14]
[71]
Buyukterzi, Z.; Can, U.; Alpaydin, S.; Guzelant, A.; Karaarslan, S.; Mustu, M.; Kocyigit, D.; Gurses, K.M. Enhanced serum levels of matrix Gla protein and bone morphogenetic protein in acute coronary syndrome patients. J. Clin. Lab. Anal., 2018, 32(3), e22278
[http://dx.doi.org/10.1002/jcla.22278] [PMID: 28605143]
[72]
Silaghi, C.N.; Fodor, D.; Cristea, V.; Crăciun, A.M. Synovial and serum levels of uncarboxylated matrix Gla-protein (ucMGP) in patients with arthritis. Clin. Chem. Lab. Med., 2011, 50(1), 125-128.
[http://dx.doi.org/10.1515/cclm.2011.713] [PMID: 21923476]
[73]
Silaghi, C.N.; Fodor, D.; Crăciun, A.M. Circulating matrix Gla protein: a potential tool to identify minor carotid stenosis with calcification in a risk population. Clin. Chem. Lab. Med., 2013, 51(5), 1115-1123.
[http://dx.doi.org/10.1515/cclm-2012-0329] [PMID: 22992285]
[74]
Silaghi, C.N.; Olteanu, G.; Crăciun, A.M. The behavior of circulating matrix Gla protein, matrix metalloproteinase-9 and nitrotyrosine in patients with varicose veins. Human and Veterinary Medicine, 2015, 7(2), 65-69.
[75]
McCullough, P.A.; Agrawal, V.; Danielewicz, E.; Abela, G.S. Accelerated atherosclerotic calcification and Monckeberg’s sclerosis: a continuum of advanced vascular pathology in chronic kidney disease. Clin. J. Am. Soc. Nephrol., 2008, 3(6), 1585-1598.
[http://dx.doi.org/10.2215/CJN.01930408] [PMID: 18667741]
[76]
Hruska, K.A.; Mathew, S.; Lund, R.; Qiu, P.; Pratt, R. Hyperphosphatemia of chronic kidney disease. Kidney Int., 2008, 74(2), 148-157.
[http://dx.doi.org/10.1038/ki.2008.130] [PMID: 18449174]
[77]
Goodman, W.G. Vascular calcification in chronic renal failure. Lancet, 2001, 358(9288), 1115-1116.
[http://dx.doi.org/10.1016/S0140-6736(01)06299-7] [PMID: 11597661]
[78]
Schurgers, L.J.; Teunissen, K.J.; Knapen, M.H.; Geusens, P.; van der Heijde, D.; Kwaijtaal, M.; van Diest, R.; Ketteler, M.; Vermeer, C. Characteristics and performance of an immunosorbent assay for human matrix Gla-protein. Clin. Chim. Acta, 2005, 351(1-2), 131-138.
[http://dx.doi.org/10.1016/j.cccn.2004.08.003] [PMID: 15563881]
[79]
Yamada, S.; Giachelli, C.M. Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho. Bone, 2017, 100, 87-93.
[http://dx.doi.org/10.1016/j.bone.2016.11.012] [PMID: 27847254]
[80]
Cranenburg, E.C.; Vermeer, C.; Koos, R.; Boumans, M-L.; Hackeng, T.M.; Bouwman, F.G.; Kwaijtaal, M.; Brandenburg, V.M.; Ketteler, M.; Schurgers, L.J. The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification. J. Vasc. Res., 2008, 45(5), 427-436.
[http://dx.doi.org/10.1159/000124863] [PMID: 18401181]
[81]
Ueland, T.; Gullestad, L.; Dahl, C.P.; Aukrust, P.; Aakhus, S.; Solberg, O.G.; Vermeer, C.; Schurgers, L.J. Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis. J. Intern. Med., 2010, 268(5), 483-492.
[http://dx.doi.org/10.1111/j.1365-2796.2010.02264.x] [PMID: 20804515]
[82]
O’Donnell, C.J.; Shea, M.K.; Price, P.A.; Gagnon, D.R.; Wilson, P.W.; Larson, M.G.; Kiel, D.P.; Hoffmann, U.; Ferencik, M.; Clouse, M.E.; Williamson, M.K.; Cupples, L.A.; Dawson-Hughes, B.; Booth, S.L. Matrix Gla protein is associated with risk factors for atherosclerosis but not with coronary artery calcification. Arterioscler. Thromb. Vasc. Biol., 2006, 26(12), 2769-2774.
[http://dx.doi.org/10.1161/01.ATV.0000245793.83158.06] [PMID: 16973975]
[83]
Schlieper, G.; Schurgers, L.; Brandenburg, V.; Reutelingsperger, C.; Floege, J. Vascular calcification in chronic kidney disease: an update. Nephrol. Dial. Transplant., 2016, 31(1), 31-39.
[http://dx.doi.org/10.1093/ndt/gfv111] [PMID: 25916871]
[84]
Price, P.A.; Faus, S.A.; Williamson, M.K. Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler. Thromb. Vasc. Biol., 1998, 18(9), 1400-1407.
[http://dx.doi.org/10.1161/01.ATV.18.9.1400] [PMID: 9743228]
[85]
Wei, F-F.; Trenson, S.; Thijs, L.; Huang, Q-F.; Zhang, Z-Y.; Yang, W-Y.; Moliterno, P.; Allegaert, K.; Boggia, J.; Janssens, S.; Verhamme, P.; Vermeer, C.; Staessen, J.A. Desphospho-uncarboxylated matrix Gla protein is a novel circulating biomarker predicting deterioration of renal function in the general population. Nephrol. Dial. Transplant., 2018, 33(7), 1122-1128.
[http://dx.doi.org/10.1093/ndt/gfx258] [PMID: 28992263]
[86]
Wei, F-F.; Drummen, N.E.; Thijs, L.; Jacobs, L.; Herfs, M.; Van’t Hoofd, C.; Vermeer, C.; Staessen, J.A. Vitamin-K-dependent protection of the renal microvasculature: histopathological studies in normal and diseased kidneys. Pulse (Basel), 2016, 4(2-3), 85-91.
[http://dx.doi.org/10.1159/000448008] [PMID: 27752480]
[87]
Fusaro, M.; Giannini, S.; Gallieni, M.; Noale, M.; Tripepi, G.; Rossini, M.; Messa, P.; Rigotti, P.; Pati, T.; Barbisoni, F.; Piccoli, A.; Aghi, A.; Alessi, M.; Bonfante, L.; Fabris, F.; Zambon, S.; Sella, S.; Iervasi, G.; Plebani, M. Calcimimetic and vitamin D analog use in hemodialyzed patients is associated with increased levels of vitamin K dependent proteins. Endocrine, 2016, 51(2), 333-341.
[http://dx.doi.org/10.1007/s12020-015-0673-z] [PMID: 26130027]
[88]
Shroff, R.C.; McNair, R.; Figg, N.; Skepper, J.N.; Schurgers, L.; Gupta, A.; Hiorns, M.; Donald, A.E.; Deanfield, J.; Rees, L.; Shanahan, C.M. Dialysis accelerates medial vascular calcification in part by triggering smooth muscle cell apoptosis. Circulation, 2008, 118(17), 1748-1757.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.108.783738] [PMID: 18838561]
[89]
Jia, G.; Stormont, R.M.; Gangahar, D.M.; Agrawal, D.K. Role of matrix Gla protein in angiotensin II-induced exacerbation of vascular calcification. Am. J. Physiol. Heart Circ. Physiol., 2012, 303(5), H523-H532.
[http://dx.doi.org/10.1152/ajpheart.00826.2011] [PMID: 22796540]
[90]
Proudfoot, D.; Skepper, J.N.; Hegyi, L.; Bennett, M.R.; Shanahan, C.M.; Weissberg, P.L. Apoptosis regulates human vascular calcification in vitro: evidence for initiation of vascular calcification by apoptotic bodies. Circ. Res., 2000, 87(11), 1055-1062.
[http://dx.doi.org/10.1161/01.RES.87.11.1055] [PMID: 11090552]
[91]
Proudfoot, D.; Shanahan, C.M. Molecular mechanisms mediating vascular calcification: role of matrix Gla protein. Nephrology (Carlton), 2006, 11(5), 455-461.
[http://dx.doi.org/10.1111/j.1440-1797.2006.00660.x] [PMID: 17014561]
[92]
Marulanda, J.; Eimar, H.; McKee, M.D.; Berkvens, M.; Nelea, V.; Roman, H.; Borrás, T.; Tamimi, F.; Ferron, M.; Murshed, M. Matrix Gla protein deficiency impairs nasal septum growth, causing midface hypoplasia. J. Biol. Chem., 2017, 292(27), 11400-11412.
[http://dx.doi.org/10.1074/jbc.M116.769802] [PMID: 28487368]
[93]
Boraldi, F.; Annovi, G.; Vermeer, C.; Schurgers, L.J.; Trenti, T.; Tiozzo, R.; Guerra, D.; Quaglino, D. Matrix gla protein and alkaline phosphatase are differently modulated in human dermal fibroblasts from PXE patients and controls. J. Invest. Dermatol., 2013, 133(4), 946-954.
[http://dx.doi.org/10.1038/jid.2012.460] [PMID: 23223140]
[94]
Jain, A.P.; Pundir, S.; Sharma, A. Bone morphogenetic proteins: The anomalous molecules. J. Indian Soc. Periodontol., 2013, 17(5), 583-586.
[http://dx.doi.org/10.4103/0972-124X.119275] [PMID: 24174749]
[95]
Beck, S.E.; Jung, B.H.; Fiorino, A.; Gomez, J.; Rosario, E.D.; Cabrera, B.L.; Huang, S.C.; Chow, J.Y.; Carethers, J.M. Bone morphogenetic protein signaling and growth suppression in colon cancer. Am. J. Physiol. Gastrointest. Liver Physiol., 2006, 291(1), G135-G145.
[http://dx.doi.org/10.1152/ajpgi.00482.2005] [PMID: 16769811]
[96]
Mendelson, J.; Song, S.; Li, Y.; Maru, D.M.; Mishra, B.; Davila, M.; Hofstetter, W.L.; Mishra, L. Dysfunctional transforming growth factor-β signaling with constitutively active Notch signaling in Barrett’s esophageal adenocarcinoma. Cancer, 2011, 117(16), 3691-3702.
[http://dx.doi.org/10.1002/cncr.25861] [PMID: 21305538]
[97]
Boström, K.; Watson, K.E.; Horn, S.; Wortham, C.; Herman, I.M.; Demer, L.L. Bone morphogenetic protein expression in human atherosclerotic lesions. J. Clin. Invest., 1993, 91(4), 1800-1809.
[http://dx.doi.org/10.1172/JCI116391] [PMID: 8473518]
[98]
Steitz, S.A.; Speer, M.Y.; Curinga, G.; Yang, H-Y.; Haynes, P.; Aebersold, R.; Schinke, T.; Karsenty, G.; Giachelli, C.M. Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ. Res., 2001, 89(12), 1147-1154.
[http://dx.doi.org/10.1161/hh2401.101070] [PMID: 11739279]
[99]
Boström, K.; Tsao, D.; Shen, S.; Wang, Y.; Demer, L.L. Matrix GLA protein modulates differentiation induced by bone morphogenetic protein-2 in C3H10T1/2 cells. J. Biol. Chem., 2001, 276(17), 14044-14052.
[http://dx.doi.org/10.1074/jbc.M008103200] [PMID: 11278388]
[100]
Tüysüz, B.; Cinar, B.; Laçiner, S.; Onay, H.; Mittaz-Crettol, L. Clinical variability in two sisters with keutel syndrome due to a homozygous mutation in mgp gene. Genet. Couns., 2015, 26(2), 187-194.
[PMID: 26349188]
[101]
Xu, L.; Xia, Z.; Liu, X.; Huang, S. A case of Keutel syndrome in child (review the literature). Lin chuang er bi yan hou tou jing wai ke za zhi, 2012, 26(18), 793-794.
[PMID: 23259292]
[102]
Bosemani, T.; Felling, R.J.; Wyse, E.; Pearl, M.S.; Tekes, A.; Ahn, E.; Poretti, A.; Huisman, T.A. Neuroimaging findings in children with Keutel syndrome. Pediatr. Radiol., 2014, 44(1), 73-78.
[http://dx.doi.org/10.1007/s00247-013-2768-0] [PMID: 23917590]
[103]
Farzaneh-Far, A.; Davies, J.D.; Braam, L.A.; Spronk, H.M.; Proudfoot, D.; Chan, S.W.; O’Shaughnessy, K.M.; Weissberg, P.L.; Vermeer, C.; Shanahan, C.M. A polymorphism of the human matrix gamma-carboxyglutamic acid protein promoter alters binding of an activating protein-1 complex and is associated with altered transcription and serum levels. J. Biol. Chem., 2001, 276(35), 32466-32473.
[http://dx.doi.org/10.1074/jbc.M104909200] [PMID: 11425864]