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Published in: Cardiovascular Diabetology 1/2014

Open Access 01-12-2014 | Original investigation

Vascular calcification in patients with type 2 diabetes: the involvement of matrix Gla protein

Authors: Sophie Liabeuf, Bourron Olivier, Cees Vemeer, Elke Theuwissen, Elke Magdeleyns, Carole Elodie Aubert, Michel Brazier, Romuald Mentaverri, Agnes Hartemann, Ziad A Massy

Published in: Cardiovascular Diabetology | Issue 1/2014

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Abstract

Background

Matrix Gla protein (MGP) is an important inhibitor of calcification. The objective of the present study of patients with type 2 diabetes and normal or slightly altered kidney function was to evaluate levels of inactive, dephospho-uncarboxylated MGP(dp-ucMGP) and total uncarboxylated MGP(t-ucMGP) and assess their links with biological and clinical parameters (including peripheral vascular calcification).

Methods

The DIACART study is a cross-sectional cohort study of 198 patients with type 2 diabetes and normal or slightly altered kidney function. Matrix Gla protein levels were measured with an ELISA and all patients underwent multislice spiral computed tomography scans to score below-knee arterial calcification.

Results

In the study population as a whole, the mean dp-ucMGP and t-ucMGP levels were 627 ± 451 pM and 4868 ± 1613 nM, respectively. Glomerular filtration rate, age and current vitamin K antagonist use were independently associated with dp-ucMGP levels. When the study population was divided according to the median peripheral arterial calcification score, patients with the higher score displayed significantly lower t-ucMGP and significantly higher dp-ucMGP levels. Furthermore, plasma dp-ucMGP was positively associated with the peripheral arterial calcification score (independently of age, gender, previous cardiovascular disease and t-ucMGP levels).

Conclusions

High dp-ucMGP levels were independently associated with below-knee arterial calcification score in patients with type 2 diabetes and normal or slightly altered kidney function. The reversibility of the elevation of dp-ucMGP levels and the latter’s relationship with clinical events merit further investigation.
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Literature
1.
go back to reference Guzman RJ, Brinkley DM, Schumacher PM, Donahue RM, Beavers H, Qin X: Tibial artery calcification as a marker of amputation risk in patients with peripheral arterial disease. J Am Coll Cardiol. 2008, 51 (20): 1967-1974. 10.1016/j.jacc.2007.12.058.PubMedCentralCrossRefPubMed Guzman RJ, Brinkley DM, Schumacher PM, Donahue RM, Beavers H, Qin X: Tibial artery calcification as a marker of amputation risk in patients with peripheral arterial disease. J Am Coll Cardiol. 2008, 51 (20): 1967-1974. 10.1016/j.jacc.2007.12.058.PubMedCentralCrossRefPubMed
2.
go back to reference Kronmal RA, McClelland RL, Detrano R, Shea S, Lima JA, Cushman M, Bild DE, Burke GL: Risk factors for the progression of coronary artery calcification in asymptomatic subjects: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2007, 115 (21): 2722-2730. 10.1161/CIRCULATIONAHA.106.674143.CrossRefPubMed Kronmal RA, McClelland RL, Detrano R, Shea S, Lima JA, Cushman M, Bild DE, Burke GL: Risk factors for the progression of coronary artery calcification in asymptomatic subjects: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2007, 115 (21): 2722-2730. 10.1161/CIRCULATIONAHA.106.674143.CrossRefPubMed
3.
go back to reference Raggi P, Cooil B, Ratti C, Callister TQ, Budoff M: Progression of coronary artery calcium and occurrence of myocardial infarction in patients with and without diabetes mellitus. Hypertension. 2005, 46 (1): 238-243. 10.1161/01.HYP.0000164575.16609.02.CrossRefPubMed Raggi P, Cooil B, Ratti C, Callister TQ, Budoff M: Progression of coronary artery calcium and occurrence of myocardial infarction in patients with and without diabetes mellitus. Hypertension. 2005, 46 (1): 238-243. 10.1161/01.HYP.0000164575.16609.02.CrossRefPubMed
4.
go back to reference Rossi A, Targher G, Zoppini G, Cicoira M, Bonapace S, Negri C, Stoico V, Faggiano P, Vassanelli C, Bonora E: Aortic and mitral annular calcifications are predictive of all-cause and cardiovascular mortality in patients with type 2 diabetes. Diabetes Care. 2012, 35 (8): 1781-1786. 10.2337/dc12-0134.PubMedCentralCrossRefPubMed Rossi A, Targher G, Zoppini G, Cicoira M, Bonapace S, Negri C, Stoico V, Faggiano P, Vassanelli C, Bonora E: Aortic and mitral annular calcifications are predictive of all-cause and cardiovascular mortality in patients with type 2 diabetes. Diabetes Care. 2012, 35 (8): 1781-1786. 10.2337/dc12-0134.PubMedCentralCrossRefPubMed
5.
go back to reference Aoki A, Murata M, Asano T, Ikoma A, Sasaki M, Saito T, Otani T, Jinbo S, Ikeda N, Kawakami M, Ishikawa SE: Association of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes. Cardiovasc Diabetol. 2013, 12: 11-10.1186/1475-2840-12-11.PubMedCentralCrossRefPubMed Aoki A, Murata M, Asano T, Ikoma A, Sasaki M, Saito T, Otani T, Jinbo S, Ikeda N, Kawakami M, Ishikawa SE: Association of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes. Cardiovasc Diabetol. 2013, 12: 11-10.1186/1475-2840-12-11.PubMedCentralCrossRefPubMed
6.
go back to reference Sheng L, Cao W, Cha B, Chen Z, Wang F, Liu J: Serum osteocalcin level and its association with carotid atherosclerosis in patients with type 2 diabetes. Cardiovasc Diabetol. 2013, 12: 22-10.1186/1475-2840-12-22.PubMedCentralCrossRefPubMed Sheng L, Cao W, Cha B, Chen Z, Wang F, Liu J: Serum osteocalcin level and its association with carotid atherosclerosis in patients with type 2 diabetes. Cardiovasc Diabetol. 2013, 12: 22-10.1186/1475-2840-12-22.PubMedCentralCrossRefPubMed
7.
go back to reference Schurgers LJ, Spronk HM, Skepper JN, Hackeng TM, Shanahan CM, Vermeer C, Weissberg PL, Proudfoot D: Post-translational modifications regulate matrix Gla protein function: importance for inhibition of vascular smooth muscle cell calcification. J Thromb Haemost. 2007, 5 (12): 2503-2511. 10.1111/j.1538-7836.2007.02758.x.CrossRefPubMed Schurgers LJ, Spronk HM, Skepper JN, Hackeng TM, Shanahan CM, Vermeer C, Weissberg PL, Proudfoot D: Post-translational modifications regulate matrix Gla protein function: importance for inhibition of vascular smooth muscle cell calcification. J Thromb Haemost. 2007, 5 (12): 2503-2511. 10.1111/j.1538-7836.2007.02758.x.CrossRefPubMed
8.
go back to reference Schurgers LJ, Uitto J, Reutelingsperger CP: Vitamin K-dependent carboxylation of matrix Gla-protein: a crucial switch to control ectopic mineralization. Trends Mol Med. 2013, 19 (4): 217-226. 10.1016/j.molmed.2012.12.008.CrossRefPubMed Schurgers LJ, Uitto J, Reutelingsperger CP: Vitamin K-dependent carboxylation of matrix Gla-protein: a crucial switch to control ectopic mineralization. Trends Mol Med. 2013, 19 (4): 217-226. 10.1016/j.molmed.2012.12.008.CrossRefPubMed
9.
go back to reference Cranenburg EC, Koos R, Schurgers LJ, Magdeleyns EJ, Schoonbrood TH, Landewe RB, Brandenburg VM, Bekers O, Vermeer C: Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species. Thromb Haemost. 2010, 104 (4): 811-822. 10.1160/TH09-11-0786.CrossRefPubMed Cranenburg EC, Koos R, Schurgers LJ, Magdeleyns EJ, Schoonbrood TH, Landewe RB, Brandenburg VM, Bekers O, Vermeer C: Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species. Thromb Haemost. 2010, 104 (4): 811-822. 10.1160/TH09-11-0786.CrossRefPubMed
10.
go back to reference Schurgers LJ, Barreto DV, Barreto FC, Liabeuf S, Renard C, Magdeleyns EJ, Vermeer C, Choukroun G, Massy ZA: The circulating inactive form of matrix gla protein is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report. Clin J Am Soc Nephrol. 2010, 5 (4): 568-575. 10.2215/CJN.07081009.PubMedCentralCrossRefPubMed Schurgers LJ, Barreto DV, Barreto FC, Liabeuf S, Renard C, Magdeleyns EJ, Vermeer C, Choukroun G, Massy ZA: The circulating inactive form of matrix gla protein is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report. Clin J Am Soc Nephrol. 2010, 5 (4): 568-575. 10.2215/CJN.07081009.PubMedCentralCrossRefPubMed
11.
go back to reference Dalmeijer GW, van der Schouw YT, Magdeleyns EJ, Vermeer C, Verschuren WM, Boer JM, Beulens JW: Matrix Gla Protein Species and Risk of Cardiovascular Events in Type 2 Diabetic Patients. Diabetes Care. 2013, 36 (11): 3766-3771. 10.2337/dc13-0065.PubMedCentralCrossRefPubMed Dalmeijer GW, van der Schouw YT, Magdeleyns EJ, Vermeer C, Verschuren WM, Boer JM, Beulens JW: Matrix Gla Protein Species and Risk of Cardiovascular Events in Type 2 Diabetic Patients. Diabetes Care. 2013, 36 (11): 3766-3771. 10.2337/dc13-0065.PubMedCentralCrossRefPubMed
12.
go back to reference Parker BD, Schurgers LJ, Vermeer C, Schiller NB, Whooley MA, Ix JH: The association of uncarboxylated matrix Gla protein with mitral annular calcification differs by diabetes status: The Heart and Soul study. Atherosclerosis. 2010, 210 (1): 320-325. 10.1016/j.atherosclerosis.2009.11.023.PubMedCentralCrossRefPubMed Parker BD, Schurgers LJ, Vermeer C, Schiller NB, Whooley MA, Ix JH: The association of uncarboxylated matrix Gla protein with mitral annular calcification differs by diabetes status: The Heart and Soul study. Atherosclerosis. 2010, 210 (1): 320-325. 10.1016/j.atherosclerosis.2009.11.023.PubMedCentralCrossRefPubMed
13.
go back to reference Thomsen SB, Rathcke CN, Zerahn B, Vestergaard H: Increased levels of the calcification marker matrix Gla Protein and the inflammatory markers YKL-40 and CRP in patients with type 2 diabetes and ischemic heart disease. Cardiovasc Diabetol. 2010, 9: 86-10.1186/1475-2840-9-86.PubMedCentralCrossRefPubMed Thomsen SB, Rathcke CN, Zerahn B, Vestergaard H: Increased levels of the calcification marker matrix Gla Protein and the inflammatory markers YKL-40 and CRP in patients with type 2 diabetes and ischemic heart disease. Cardiovasc Diabetol. 2010, 9: 86-10.1186/1475-2840-9-86.PubMedCentralCrossRefPubMed
14.
go back to reference Silaghi CN, Fodor D, Craciun AM: 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.CrossRefPubMed Silaghi CN, Fodor D, Craciun AM: 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.CrossRefPubMed
15.
go back to reference Doyon M, Mathieu P, Moreau P: Decreased expression of gamma-carboxylase in diabetes-associated arterial stiffness: impact on matrix Gla protein. Cardiovasc Res. 2013, 97 (2): 331-338. 10.1093/cvr/cvs325.CrossRefPubMed Doyon M, Mathieu P, Moreau P: Decreased expression of gamma-carboxylase in diabetes-associated arterial stiffness: impact on matrix Gla protein. Cardiovasc Res. 2013, 97 (2): 331-338. 10.1093/cvr/cvs325.CrossRefPubMed
16.
go back to reference Schurgers LJ, Teunissen KJ, Knapen MH, Kwaijtaal M, van Diest R, Appels A, Reutelingsperger CP, Cleutjens JP, Vermeer C: Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein: undercarboxylated matrix Gla protein as marker for vascular calcification. Arterioscler Thromb Vasc Biol. 2005, 25 (8): 1629-1633. 10.1161/01.ATV.0000173313.46222.43.CrossRefPubMed Schurgers LJ, Teunissen KJ, Knapen MH, Kwaijtaal M, van Diest R, Appels A, Reutelingsperger CP, Cleutjens JP, Vermeer C: Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein: undercarboxylated matrix Gla protein as marker for vascular calcification. Arterioscler Thromb Vasc Biol. 2005, 25 (8): 1629-1633. 10.1161/01.ATV.0000173313.46222.43.CrossRefPubMed
17.
go back to reference Schurgers LJ, Spronk HM, Soute BA, Schiffers PM, DeMey JG, Vermeer C: Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats. Blood. 2007, 109 (7): 2823-2831.PubMed Schurgers LJ, Spronk HM, Soute BA, Schiffers PM, DeMey JG, Vermeer C: Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats. Blood. 2007, 109 (7): 2823-2831.PubMed
18.
go back to reference Shroff RC, McNair R, Figg N, Skepper JN, Schurgers L, Gupta A, Hiorns M, Donald AE, Deanfield J, Rees L, Shanahan CM: Dialysis accelerates medial vascular calcification in part by triggering smooth muscle cell apoptosis. Circulation. 2008, 118 (17): 1748-1757. 10.1161/CIRCULATIONAHA.108.783738.CrossRefPubMed Shroff RC, McNair R, Figg N, Skepper JN, Schurgers L, Gupta A, Hiorns M, Donald AE, Deanfield J, Rees L, Shanahan CM: Dialysis accelerates medial vascular calcification in part by triggering smooth muscle cell apoptosis. Circulation. 2008, 118 (17): 1748-1757. 10.1161/CIRCULATIONAHA.108.783738.CrossRefPubMed
19.
go back to reference Cranenburg EC, Vermeer C, Koos R, Boumans ML, Hackeng TM, Bouwman FG, Kwaijtaal M, Brandenburg VM, Ketteler M, Schurgers LJ: The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification. J Vasc Res. 2008, 45 (5): 427-436. 10.1159/000124863.CrossRefPubMed Cranenburg EC, Vermeer C, Koos R, Boumans ML, Hackeng TM, Bouwman FG, Kwaijtaal M, Brandenburg VM, Ketteler M, Schurgers LJ: The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification. J Vasc Res. 2008, 45 (5): 427-436. 10.1159/000124863.CrossRefPubMed
20.
go back to reference Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R: Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990, 15 (4): 827-832. 10.1016/0735-1097(90)90282-T.CrossRefPubMed Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R: Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990, 15 (4): 827-832. 10.1016/0735-1097(90)90282-T.CrossRefPubMed
21.
go back to reference Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G: Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature. 1997, 386 (6620): 78-81. 10.1038/386078a0.CrossRefPubMed Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G: Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature. 1997, 386 (6620): 78-81. 10.1038/386078a0.CrossRefPubMed
22.
go back to reference Jia G, Stormont RM, Gangahar DM, Agrawal DK: Role of matrix Gla protein in angiotensin II-induced exacerbation of vascular calcification. Am J Physiol Heart Circ Physiol. 2012, 303 (5): H523-H532. 10.1152/ajpheart.00826.2011.PubMedCentralCrossRefPubMed Jia G, Stormont RM, Gangahar DM, Agrawal DK: Role of matrix Gla protein in angiotensin II-induced exacerbation of vascular calcification. Am J Physiol Heart Circ Physiol. 2012, 303 (5): H523-H532. 10.1152/ajpheart.00826.2011.PubMedCentralCrossRefPubMed
23.
go back to reference Wajih N, Borras T, Xue W, Hutson SM, Wallin R: Processing and transport of matrix gamma-carboxyglutamic acid protein and bone morphogenetic protein-2 in cultured human vascular smooth muscle cells: evidence for an uptake mechanism for serum fetuin. J Biol Chem. 2004, 279 (41): 43052-43060. 10.1074/jbc.M407180200.CrossRefPubMed Wajih N, Borras T, Xue W, Hutson SM, Wallin R: Processing and transport of matrix gamma-carboxyglutamic acid protein and bone morphogenetic protein-2 in cultured human vascular smooth muscle cells: evidence for an uptake mechanism for serum fetuin. J Biol Chem. 2004, 279 (41): 43052-43060. 10.1074/jbc.M407180200.CrossRefPubMed
24.
go back to reference Boxma PY, van den Berg E, Geleijnse JM, Laverman GD, Schurgers LJ, Vermeer C, Kema IP, Muskiet FA, Navis G, Bakker SJ, De Borst MH: Vitamin k intake and plasma desphospho-uncarboxylated matrix Gla-protein levels in kidney transplant recipients. PLoS One. 2013, 7 (10): e47991.CrossRef Boxma PY, van den Berg E, Geleijnse JM, Laverman GD, Schurgers LJ, Vermeer C, Kema IP, Muskiet FA, Navis G, Bakker SJ, De Borst MH: Vitamin k intake and plasma desphospho-uncarboxylated matrix Gla-protein levels in kidney transplant recipients. PLoS One. 2013, 7 (10): e47991.CrossRef
25.
go back to reference Flammer AJ, Gossl M, Li J, Matsuo Y, Reriani M, Loeffler D, Simari RD, Lerman LO, Khosla S, Lerman A: Patients with an HbA1c in the prediabetic and diabetic range have higher numbers of circulating cells with osteogenic and endothelial progenitor cell markers. J Clin Endocrinol Metab. 2012, 97 (12): 4761-4768. 10.1210/jc.2012-2642.PubMedCentralCrossRefPubMed Flammer AJ, Gossl M, Li J, Matsuo Y, Reriani M, Loeffler D, Simari RD, Lerman LO, Khosla S, Lerman A: Patients with an HbA1c in the prediabetic and diabetic range have higher numbers of circulating cells with osteogenic and endothelial progenitor cell markers. J Clin Endocrinol Metab. 2012, 97 (12): 4761-4768. 10.1210/jc.2012-2642.PubMedCentralCrossRefPubMed
26.
go back to reference Fadini GP, Albiero M, Menegazzo L, Boscaro E, Vigili De Kreutzenberg S, Agostini C, Cabrelle A, Binotto G, Rattazzi M, Bertacco E, Bertorelle R, Biasini L, Mion M, Plebani M, Ceolotto G, Angelini A, Castellani C, Menegolo M, Grego F, Dimmeler S, Seeger F, Zeiher A, Tiengo A, Avogaro A: Widespread increase in myeloid calcifying cells contributes to ectopic vascular calcification in type 2 diabetes. Circ Res. 2011, 108 (9): 1112-1121. 10.1161/CIRCRESAHA.110.234088.CrossRefPubMed Fadini GP, Albiero M, Menegazzo L, Boscaro E, Vigili De Kreutzenberg S, Agostini C, Cabrelle A, Binotto G, Rattazzi M, Bertacco E, Bertorelle R, Biasini L, Mion M, Plebani M, Ceolotto G, Angelini A, Castellani C, Menegolo M, Grego F, Dimmeler S, Seeger F, Zeiher A, Tiengo A, Avogaro A: Widespread increase in myeloid calcifying cells contributes to ectopic vascular calcification in type 2 diabetes. Circ Res. 2011, 108 (9): 1112-1121. 10.1161/CIRCRESAHA.110.234088.CrossRefPubMed
27.
go back to reference Johnson RC, Leopold JA, Loscalzo J: Vascular calcification: pathobiological mechanisms and clinical implications. Circ Res. 2006, 99 (10): 1044-1059. 10.1161/01.RES.0000249379.55535.21.CrossRefPubMed Johnson RC, Leopold JA, Loscalzo J: Vascular calcification: pathobiological mechanisms and clinical implications. Circ Res. 2006, 99 (10): 1044-1059. 10.1161/01.RES.0000249379.55535.21.CrossRefPubMed
28.
go back to reference Price PA, Faus SA, Williamson MK: Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler Thromb Vasc Biol. 1998, 18 (9): 1400-1407. 10.1161/01.ATV.18.9.1400.CrossRefPubMed Price PA, Faus SA, Williamson MK: Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler Thromb Vasc Biol. 1998, 18 (9): 1400-1407. 10.1161/01.ATV.18.9.1400.CrossRefPubMed
29.
go back to reference Chatrou ML, Winckers K, Hackeng TM, Reutelingsperger CP, Schurgers LJ: Vascular calcification: the price to pay for anticoagulation therapy with vitamin K-antagonists. Blood Rev. 2012, 26 (4): 155-166. 10.1016/j.blre.2012.03.002.CrossRefPubMed Chatrou ML, Winckers K, Hackeng TM, Reutelingsperger CP, Schurgers LJ: Vascular calcification: the price to pay for anticoagulation therapy with vitamin K-antagonists. Blood Rev. 2012, 26 (4): 155-166. 10.1016/j.blre.2012.03.002.CrossRefPubMed
30.
go back to reference Holden RM, Morton AR, Garland JS, Pavlov A, Day AG, Booth SL: Vitamins K and D status in stages 3–5 chronic kidney disease. Clin J Am Soc Nephrol. 2010, 5 (4): 590-597. 10.2215/CJN.06420909.PubMedCentralCrossRefPubMed Holden RM, Morton AR, Garland JS, Pavlov A, Day AG, Booth SL: Vitamins K and D status in stages 3–5 chronic kidney disease. Clin J Am Soc Nephrol. 2010, 5 (4): 590-597. 10.2215/CJN.06420909.PubMedCentralCrossRefPubMed
31.
go back to reference Krueger T, Westenfeld R, Ketteler M, Schurgers LJ, Floege J: Vitamin K deficiency in CKD patients: a modifiable risk factor for vascular calcification?. Kidney Int. 2009, 76 (1): 18-22. 10.1038/ki.2009.126.CrossRefPubMed Krueger T, Westenfeld R, Ketteler M, Schurgers LJ, Floege J: Vitamin K deficiency in CKD patients: a modifiable risk factor for vascular calcification?. Kidney Int. 2009, 76 (1): 18-22. 10.1038/ki.2009.126.CrossRefPubMed
32.
go back to reference Westenfeld R, Krueger T, Schlieper G, Cranenburg EC, Magdeleyns EJ, Heidenreich S, Holzmann S, Vermeer C, Jahnen-Dechent W, Ketteler M, Floege J, Schurgers LJ: Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis. 2012, 59 (2): 186-195. 10.1053/j.ajkd.2011.10.041.CrossRefPubMed Westenfeld R, Krueger T, Schlieper G, Cranenburg EC, Magdeleyns EJ, Heidenreich S, Holzmann S, Vermeer C, Jahnen-Dechent W, Ketteler M, Floege J, Schurgers LJ: Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis. 2012, 59 (2): 186-195. 10.1053/j.ajkd.2011.10.041.CrossRefPubMed
Metadata
Title
Vascular calcification in patients with type 2 diabetes: the involvement of matrix Gla protein
Authors
Sophie Liabeuf
Bourron Olivier
Cees Vemeer
Elke Theuwissen
Elke Magdeleyns
Carole Elodie Aubert
Michel Brazier
Romuald Mentaverri
Agnes Hartemann
Ziad A Massy
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2014
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-13-85

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