Abstract
Background: Calcific aortic valve disease (CAVD) is a major contributor to cardiovascular morbidity and mortality. Circulating total uncarboxylated Matrix ?-carboxyglutamate (Gla) protein (t-ucMGP) is a promising biomarker for rapid screening of subjects prone to cardiovascular calcification who may need more invasive vascular diagnostics. Preliminary data show that low t-ucMGP levels are indicative for prevalent vascular calcification. Hence, the aim of our study was to investigate the possible role of circulating t-ucMGP as a biomarker may help in identification patients with CAVD, taking into consideration that CAVD is a form of vascular calcification.
Methods & Materials: We analyzed serum t-ucMGP levels by enzyme-linked immunosorbent assay (ELISA) in 50 patients with echocardiographically proven CAVD and 21 control subjects.
Results: Serum t-ucMGP levels were significantly lower in patients with CAVD (29.29±12.18 nmol/l) compared to the control group (36.84±21.79 nmol/l, p = 0.003).
Conclusion: Serum t-ucMGP may help as a noninvasive biomarker for identification of these patients.
References
Mathieu P, Boulanger M-C, Bouchareb R. Molecular biology of calcific aortic valve disease: Towards new pharmacological therapies. Expert Rev Cardiovasc Ther 2014; 12(7): 851-62.
https://doi.org/10.1586/14779072.2014.923756
O'Brien KD. Pathogenesis of calcific aortic valve disease: A disease process comes of age (and a good deal more). Arterioscler Thromb Vasc Biol 2006; 26(8): 1721-8.
https://doi.org/10.1161/01.ATV.0000227513.13697.ac
Sainger R, Grau JB, Branchetti E, Poggio P, Lai E, Koka E, et al. Comparison of transesophageal echocardiographic analysis and circulating biomarker expression profile in calcific aortic valve disease. J Heart Valve Dis 2013; 22(2): 156-65.
Beckmann E, Grau JB, Sainger R, Poggio P, Ferrari G. Insights into the use of biomarkers in calcific aortic valve disease. J Heart Valve Dis 2010; 19(4): 441-52.
Mathieu P, Boulanger M-C. Basic mechanisms of calcific aortic valve disease. Can J Cardiol 2014; 30(9): 982-93.
https://doi.org/10.1016/j.cjca.2014.03.029
Towler DA. Molecular and cellular aspects of calcific aortic valve disease. Circ Res 2013; 113(2): 198-208.
https://doi.org/10.1161/CIRCRESAHA.113.300155
Freeman RV, Otto CM. Spectrum of calcific aortic valve disease: Pathogenesis, disease progression, and treatment Strategies. Circulation. 2005; 111(24): 3316-26.
https://doi.org/10.1161/CIRCULATIONAHA.104.486738
Zeng Y, Sun R, Li X, Liu M, Chen S, Zhang P. Pathophysiology of valvular heart disease (Review). Exp Ther Med 2016; 11(4): 1184-8.
https://doi.org/10.3892/etm.2016.3048
Dweck MR, Boon NA, Newby DE. Calcific aortic stenosis: A disease of the valve and the myocardium. J Am Coll Cardiol 2012; 60(19): 1854-63.
https://doi.org/10.1016/j.jacc.2012.02.093
Leopold JA. Cellular mechanisms of aortic valve calcification. Circ Cardiovasc Interv 2012; 5(4): 605-14.
https://doi.org/10.1161/CIRCINTERVENTIONS.112.971028
Bostrom KI, Rajamannan NM, Towler DA. The regulation of valvular and vascular sclerosis by osteogenic morphogens. Circ Res 2011; 109(5): 564-77.
https://doi.org/10.1161/CIRCRESAHA.110.234278
Bossé Y, Mathieu P, Pibarot P. Genomics: The next step to elucidate the etiology of calcific aortic valve stenosis. J Am Coll Cardiol 2008; 51(14): 1327-36.
https://doi.org/10.1016/j.jacc.2007.12.031
Fusaro M, Crepaldi G, Maggi S, Galli F, D'Angelo A, Calò L, et al. Vitamin K, bone fractures, and vascular calcifications in chronic kidney disease: An important but poorly studied relationship. J Endocrinol Invest 2011; 34(4): 317-23.
https://doi.org/10.1007/BF03347093
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): 217-26.
https://doi.org/10.1016/j.molmed.2012.12.008
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): 2823-31.
Hackeng TM, Rosing J, Spronk HMH, Vermeer C. Total chemical synthesis of human matrix Gla protein. Protein Sci 2001; 10(4): 864-70.
https://doi.org/10.1110/ps.44701
Schurgers LJ, Barreto DV, Barreto FC, Liabeuf S, Renard C, Magdeleyns EJ, et al. 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): 568-75.
https://doi.org/10.2215/CJN.07081009
Epstein M. Matrix Gla-protein (MGP) not only inhibits calcification in large arteries but also may be renoprotective: Connecting the dots. EBioMedicine 2016; 4: 16-7.
https://doi.org/10.1016/j.ebiom.2016.01.026
Schurgers LJ, Cranenburg ECM, Vermeer C. Matrix Gla-protein: The calcification inhibitor in need of vitamin K. Thromb Haemost 2008; 100(4): 593-603.
Proudfoot D, Shanahan CM. Molecular mechanisms mediating vascular calcification: Role of matrix Gla protein. Nephrology. 2006; 11(5): 455-61.
https://doi.org/10.1111/j.1440-1797.2006.00660.x
Mayer O, Seidlerová J, Bruthans J, Filipovský J, Timoracká K, Vanek J, et al. Desphospho-uncarboxylated matrix Gla-protein is associated with mortality risk in patients with chronic stable vascular disease. Atherosclerosis 2014; 235(1): 162-8.
https://doi.org/10.1016/j.atherosclerosis.2014.04.027
Cranenburg EC, Vermeer C, Koos R, Boumans ML, Hackeng TM, Bouwman FG, et al. The circulating inactive form of matrix Gla Protein (ucMGP) as a biomarker for cardiovascular calcification. J Vasc Res 2008; 45(5): 427-36.
https://doi.org/10.1159/000124863
Schurgers LJ, Teunissen KJ, Knapen M, Kwaijtaal M, van Diest R, Appels A, et al. 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: 1629-33.
https://doi.org/10.1161/01.ATV.0000173313.46222.43
Theuwissen E, Smit E, Vermeer C. The role of vitamin K in soft-tissue calcification. Adv Nutr 2012; 3(2): 166-73.
https://doi.org/10.3945/an.111.001628
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): 1400-7.
https://doi.org/10.1161/01.ATV.18.9.1400
Venardos N, Bennett D, Weyant MJ, Reece TB, Meng X, Fullerton DA. Matrix Gla protein regulates calcification of the aortic valve. J Surg Res 2015; 199(1): 1-6.
https://doi.org/10.1016/j.jss.2015.04.076
Koos R, Krueger T, Westenfeld R, Kühl HP, Brandenburg V, Mahnken AH, et al. Relation of circulating matrix Gla-protein and anticoagulation status in patients with aortic valve calcification. Thromb Haemost 2009; 101(04): 706-13.
https://doi.org/10.1160/TH08-09-0611
Cranenburg ECM, Schurgers LJ, Magdeleyns EJ, Vermeer C, Koos R, Brandenburg VM, et al. Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species. Thromb Haemost 2010; 104(4): 811-22.
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