[en] Vascular calcification is a marker of cardiovascular risk increase. Age and specific disease such as diabetes or chronic kidney disease are important factors for calcification genesis. Vascular calcification process is a complex phenomenon, involving several activators and inhibitors factors. Indeed, recent works related to in vitro and in vivo experimental studies have led to a better understanding of calcification process and identification of molecules able to modulate this system. This revue will summarize some of these molecules with a particular interest of those with therapeutic relevance. We will present: i) calcium sensing receptor and its modulation by cinacalcet; ii) pyrophosphate supplementation; iii) fetuin A and overall propensity serum test for calcification and finally; iv) matrix-Gla-protein and the use of vitamin K to prevent vascular calcification progression.
Disciplines :
Laboratory medicine & medical technology
Author, co-author :
Liabeuf, Sophie
DELANAYE, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > Service de néphrologie
Cavalier, Etienne ; Université de Liège > Département de pharmacie > Chimie médicale
Guerin, Alain
Kamel, Said
Massy, Ziad A.
Language :
French
Title :
Inhibiteurs des calcifications cardiovasculaires.
Alternative titles :
[en] Cardiovascular calcification inhibitors
Publication date :
June 2015
Journal title :
Annales de Biologie Clinique
ISSN :
0003-3898
eISSN :
1950-6112
Publisher :
John Libbey Eurotext, France
Volume :
73
Issue :
3
Pages :
315-22
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Groupe de travail : J. Arnaud and Ph. Zaoui, CHU Grenoble ; M.C. Carlier, M. Laville and D. Fouque CHU Lyon ; E. Cavalier and P. Delanaye, CHU Sart-Tilaman Liège ; J.P. Cristol and A.S. Bargnoux, CHU Montpellier ; S. Kamel, Université de Picardie, Z. Massy, Ambroise Paré et UVSQ Paris ; et Inserm U-1088 et Université de Picardie, D. Prié, P. Urena-Torres and J.C. Souberbielle, Inserm/Université U 845 ; A. Boutten, APHP - GH Paris Nord Val de Seine ; A. Guérin, CH de Manhes ; T. Hannedouche, CHU Strasbourg, Ph. Brunet CHU Marseille ; G. Jean, Nephrocare Tassin-Charcot ; M.H. Lafage-Proust CHU St Etienne ; G. London, Inserm U970 ; L. Mercadal, Pitié Salpêtrière Paris ; L. Pieroni, CH Avignon
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Bibliography
Alexopoulos N, Raggi P. Calcification in atherosclerosis. Nat Rev Cardiol 2009;6:681-8.
Johnson RC, Leopold JA, Loscalzo J. Vascular calcification : pathobiological mechanisms and clinical implications. Circ Res 2006; 99 : 1044-59.
McCullough PA, Agrawal V, Danielewicz E, Abela GS. Accelerated atherosclerotic calcification and monckeberg's sclerosis : a continuum of advanced vascular pathology in chronic kidney disease. Clin J Am Soc Nephrol 2008; 3 : 1585-98.
Temmar M, Liabeuf S, Renard C, Czernichow S, Esper NE, Shahapuni I, et al. Pulse wave velocity and vascular calcification at different stages of chronic kidney disease. J Hypertens 2010; 28 : 163-9.
Shanahan CM. Mechanisms of vascular calcification in ckd-evidence for premature ageing ? Nat Rev Nephrol 2013; 9 : 661-70.
Sage AP, Tintut Y, Demer LL. Regulatory mechanisms in vascular calcification. Nat Rev Nephrol 2010; 7 : 528-36.
Shao JS, Cheng SL, Sadhu J, Towler DA. Inflammation and the osteogenic regulation of vascular calcification : a review and perspective. Hypertension 2010; 55 : 579-92.
Brown EM, MacLeod RJ. Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev 2001; 81 : 239-97.
Ziegelstein RC, Xiong Y, He C, Hu Q. Expression of a functional extracellular calcium-sensing receptor in human aortic endothelial cells. Biochem Biophys Res Commun 2006; 342 : 153-63.
Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004; 15 : 2208-18.
Ivanovski O, Nikolov IG, Joki N, Caudrillier A, Phan O, Mentaverri R, et al. The calcimimetic r-568 retards uremia-enhanced vascular calcification and atherosclerosis in apolipoprotein e deficient (apoe-/-) mice. Atherosclerosis 2009; 205 : 55-62.
Koleganova N, Piecha G, Ritz E, Schmitt CP, Gross ML. A calcimimetic (r-568), but not calcitriol, prevents vascular remodeling in uremia. Kidney Int 2009; 75 : 60-71.
Henaut L, Boudot C, Massy ZA, Lopez-Fernandez I, Dupont S, Mary A, et al. Calcimimetics increase casr expression and reduce mineralization in vascular smooth muscle cells : mechanisms of action. Cardiovasc Res 2014; 101 : 256-65.
Raggi P, Chertow GM, Torres PU, Csiky B, Naso A, Nossuli K, et al. The advance study : a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin d on vascular calcification in patients on hemodialysis. Nephrol Dial Transplant 2011; 26 : 1327-39.
Evolve Trial investigators, Chertow GM, Block GA, Correa-Rotter R, Drueke TB, Floege J, et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med 2012; 367 : 2482-94.
Delanaye P, Krzesinski JM, Cavalier E. Evolve : between disappointment and optimism. Nephrol Ther 2013; 9 : 241-5.
Fleisch H, Bisaz S. The inhibitory role of pyrophosphate in calcification. J Physiol (Paris) 1962; 54 : 340-1.
Lomashvili KA, Cobbs S, Hennigar RA, Hardcastle KI, O'Neill WC. Phosphate-induced vascular calcification : role of pyrophosphate and osteopontin. J Am Soc Nephrol 2004; 15 : 1392-401.
Johnson K, Polewski M, van Etten D, Terkeltaub R. Chondrogenesis mediated by ppi depletion promotes spontaneous aortic calcification in npp1-/- mice. Arterioscler Thromb Vasc Bio 2005; 25 : 686-91.
Lomashvili KA, Narisawa S, Millan JL, O'Neill WC. Vascular calcification is dependent on plasma levels of pyrophosphate. Kidney Int 2014; 85 : 1351-6.
Rutsch F, Ruf N, Vaingankar S, Toliat MR, Suk A, Hohne W, et al. Mutations in enpp1 are associated with 'idiopathic' infantile arterial calcification. Nat Genet 2003; 34 : 379-81.
Fedde KN, Blair L, Silverstein J, Coburn SP, Ryan LM, Weinstein RS, et al. Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia. J Bone Miner Res 1999; 14 : 2015-26.
Jung A, Russel RG, Bisaz S, Morgan DB, Fleisch H. Fate of intravenously injected pyrophosphate-32p in dogs. Am J Physiol 1970; 218 : 1757-64.
O'Neill WC, Lomashvili KA, Malluche HH, Faugere MC, Riser BL. Treatment with pyrophosphate inhibits uremic vascular calcification. Kidney Int 2011; 79 : 512-7.
Riser BL, Barreto FC, Rezg R, Valaitis PW, Cook CS, White JA, et al. Daily peritoneal administration of sodium pyrophosphate in a dialysis solution prevents the development of vascular calcification in a mouse model of uraemia. Nephrol Dial Transplant 2011; 26 : 3349-57.
Mori K, Emoto M, Inaba M. Fetuin-a and the cardiovascular system. Adv Clin Chem 2012; 56 : 175-95.
Reynolds JL, Skepper JN, McNair R, Kasama T, Gupta K, Weissberg PL, et al. Multifunctional roles for serum protein fetuin-a in inhibition of human vascular smooth muscle cell calcification. J Am Soc Nephrol 2005; 16 : 2920-30.
Chen NX, O'Neill KD, Chen X, Duan D, Wang E, Sturek MS, et al. Fetuin-a uptake in bovine vascular smooth muscle cells is calcium dependent and mediated by annexins. Am J Physiol Renal Physiol 2007; 292 : F599-606.
Jahnen-Dechent W, Schinke T, Trindl A, Muller-Esterl W, Sablitzky F, Kaiser S, et al. Cloning and targeted deletion of the mouse fetuin gene. J Biol Chem 1997; 272 : 31496-503.
Kuro OM. A phosphate-centric paradigm for pathophysiology and therapy of chronic kidney disease. Kidney Int Suppl (2011) 2013 ; 3 : 420-6.
Suliman ME, Garcia-Lopez E, Anderstam B, Lindholm B, Stenvinkel P. Vascular calcification inhibitors in relation to cardiovascular disease with special emphasis on fetuin-a in chronic kidney disease. Adv Clin Chem 2008; 46 : 217-62.
Liabeuf S, Okazaki H, Desjardins L, Fliser D, Goldsmith D, Covic A, et al. Vascular calcification in chronic kidney disease : are biomarkers useful for probing the pathobiology and the health risks of this process in the clinical scenario ? Nephrol Dial Transplant 2014; 29 : 1275-84.
El-Shehaby AM, Zakaria A, El-Khatib M, Mostafa N. Association of fetuin-a and cardiac calcification and inflammation levels in hemodialysis patients. Scand J Clin Lab Invest 2010; 70 : 575-82.
Jung HH, Baek HJ, Kim SW. Fetuin-a, coronary artery calcification and outcome in maintenance hemodialysis patients. Clin Nephrol 2011; 75 : 391-6.
Wang AY, Woo J, Lam CW, Wang M, Chan IH, Gao P, et al. Associations of serum fetuin-a with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol Dial Transplant 2005; 20 : 1676-85.
Moe SM, Reslerova M, Ketteler M, O'Neill K, Duan D, Koczman J, et al. Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (ckd). Kidney Int 2005; 67 : 2295-304.
Ketteler M, Bongartz P, Westenfeld R, Wildberger JE, Mahnken AH, Bohm R, et al. Association of low fetuin-a (ahsg) concentrations in serum with cardiovascular mortality in patients on dialysis : a cross-sectional study. Lancet 2003; 361 : 827-33.
Emoto M, Mori K, Lee E, Kawano N, Yamazaki Y, Tsuchikura S, et al. Fetuin-a and atherosclerotic calcified plaque in patients with type 2 diabetes mellitus. Metabolism 2010; 59 : 873-8.
Ix JH, Chertow GM, Shlipak MG, Brandenburg VM, Ketteler M, Whooley MA. Association of fetuin-a with mitral annular calcification and aortic stenosis among persons with coronary heart disease : data from the heart and soul study. Circulation 2007; 115 : 2533-9.
Mori K, Ikari Y, Jono S, Emoto M, Shioi A, Koyama H, et al. Fetuina is associated with calcified coronary artery disease. Coron Artery Dis 2010; 21 : 281-5.
Hermans MM, Brandenburg V, Ketteler M, Kooman JP, van der Sande FM, Gladziwa U, et al. Study on the relationship of serum fetuin-a concentration with aortic stiffness in patients on dialysis. Nephrol Dial Transplant 2006; 21 : 1293-9.
Mikami S, Hamano T, Fujii N, Nagasawa Y, Isaka Y, Moriyama T, et al. Serum osteoprotegerin as a screening tool for coronary artery calcification score in diabetic pre-dialysis patients. Hypertens Res 2008; 31 : 1163-70.
Ix JH, Shlipak MG, Sarnak MJ, Beck GJ, Greene T, Wang X, et al. Fetuin-a is not associated with mortality in chronic kidney disease. Kidney Int 2007; 72 : 1394-9.
Hamano T, Matsui I, Mikami S, Tomida K, Fujii N, Imai E, et al. Fetuin-mineral complex reflects extraosseous calcification stress in ckd. J Am Soc Nephrol 2010; 21 : 1998-2007.
Smith ER, Ford ML, Tomlinson LA, Rajkumar C, McMahon LP, Holt SG. Phosphorylated fetuin-a-containing calciprotein particles are associated with aortic stiffness and a procalcific milieu in patients with pre-dialysis ckd. Nephrol Dial Transplant 2012; 27 : 1957-66.
Pasch A, Farese S, Graber S, Wald J, Richtering W, Floege J, et al. Nanoparticle-based test measures overall propensity for calcification in serum. J Am Soc Nephrol 2012; 23 : 1744-52.
Smith ER, Ford ML, Tomlinson LA, Bodenham E, McMahon LP, Farese S, et al. Serum calcification propensity predicts all-cause mortality in predialysis ckd. J Am Soc Nephrol 2014; 25 : 339-48.
Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix gla protein. Nature 1997; 386 : 78-81.
Price PA, Williamson MK. Primary structure of bovine matrix gla protein, a new vitamin k-dependent bone protein. J Biol Chem 1985; 260 : 14971-5.
Price PA, Urist MR, Otawara Y. Matrix gla protein, a new gammacarboxyglutamic acid-containing protein which is associated with the organic matrix of bone. Biochem Biophys Res Commun 1983; 117 : 765-71.
Schurgers LJ, Spronk HM, Skepper JN, Hackeng TM, Shanahan CM, Vermeer C, et al. Post-translational modifications regulate matrix gla protein function : importance for inhibition of vascular smooth muscle cell calcification. J Thromb Haemost 2007; 5 : 2503-11.
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 : 1400-7.
Price PA, Chan WS, Jolson DM, Williamson MK. The elastic lamellae of devitalized arteries calcify when incubated in serum : evidence for a serum calcification factor. Arterioscler Thromb Vasc Biol 2006; 26 : 1079-85.
Lomashvili KA, Wang X, Wallin R, O'Neill WC. Matrix gla protein metabolism in vascular smooth muscle and role in uremic vascular calcification. J Biol Chem 2011; 286 : 28715-22.
Zebboudj AF, Imura M, Bostrom K. Matrix gla protein, a regulatory protein for bone morphogenetic protein-2. J Biol Chem 2002; 277 : 4388-94.
Bostrom K, Tsao D, Shen S, Wang Y, Demer LL. Matrix gla protein modulates differentiation induced by bone morphogenetic protein-2 in c3h10t1/2 cells. J Biol Chem 2001; 276 : 14044-52.
Sweatt A, Sane DC, Hutson SM, Wallin R. Matrix gla protein (mgp) and bone morphogenetic protein-2 in aortic calcified lesions of aging rats. J Thromb Haemost 2003; 1 : 178-85.
Nakagawa Y, Ikeda K, Akakabe Y, Koide M, Uraoka M, Yutaka KT, et al. Paracrine osteogenic signals via bone morphogenetic protein-2 accelerate the atherosclerotic intimal calcification in vivo. Arterioscler Thromb Vasc Biol 2010; 30 : 1908-15.
Yao Y, Bennett BJ, Wang X, Rosenfeld ME, Giachelli C, Lusis AJ, et al. Inhibition of bone morphogenetic proteins protects against atherosclerosis and vascular calcification. Circ Res 2010; 107 : 485-94.
Mori K, Yamaguchi T, Maeda M. Mechanism of 201thallium-chloride uptake in tumor cells and its relationship to potassium channels. Neurol Res 1998; 20 : 19-22.
Proudfoot D, Skepper JN, Shanahan CM, Weissberg PL. Calcification of human vascular cells in vitro is correlated with high levels of matrix gla protein and low levels of osteopontin expression. Arterioscler Thromb Vasc Biol 1998; 18 : 379-88.
Schurgers LJ, Teunissen KJ, Knapen MH, 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.
Dhore CR, Cleutjens JP, Lutgens E, Cleutjens KB, Geusens PP, Kitslaar PJ, et al. Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol 2001; 21 : 1998-2003.
Otawara Y, Price PA. Developmental appearance of matrix gla protein during calcification in the rat. J Biol Chem 1986; 261 : 10828-32.
Braam LA, Dissel P, Gijsbers BL, Spronk HM, Hamulyak K, Soute BA, et al. Assay for human matrix gla protein in serum : potential applications in the cardiovascular field. Arterioscler Thromb Vasc Biol 2000; 20 : 1257-61.
Shanahan CM, Cary NR, Salisbury JR, Proudfoot D, Weissberg PL, Edmonds ME. Medial localization of mineralization-regulating proteins in association with monckeberg's sclerosis : evidence for smooth muscle cell-mediated vascular calcification. Circulation 1999; 100 : 2168-76.
Kramann R, Brandenburg VM, Schurgers LJ, Ketteler M, Westphal S, Leisten I, et al. Novel insights into osteogenesis and matrix remodelling associated with calcific uraemic arteriolopathy. Nephrol Dial Transplant 2013; 28 : 856-68.
Cranenburg EC, Koos R, Schurgers LJ, Magdeleyns EJ, Schoonbrood TH, Landewe RB, et al. Characterisation and potential diagnostic value of circulating matrix gla protein (mgp) species. Thromb Haemost 2010; 104 : 811-22.
Schlieper G, Westenfeld R, Kruger T, Cranenburg EC, Magdeleyns EJ, Brandenburg VM, et al. Circulating nonphosphorylated carboxylated matrix gla protein predicts survival in esrd. J Am Soc Nephrol 2011; 22 : 387-95.
Schurgers LJ, Cranenburg EC, Vermeer C. Matrix gla-protein : the calcification inhibitor in need of vitamin K. Thromb Haemost 2008; 100 : 593-603.
Murshed M, Schinke T, McKee MD, Karsenty G. Extracellular matrix mineralization is regulated locally; different roles of two gla-containing proteins. J Cell Biol 2004; 165 : 625-30.
Vermeer C. Gamma-carboxyglutamate-containing proteins and the vitamin K-dependent carboxylase. Biochem J 1990; 266 : 625-36.
Schurgers LJ. Vitamin K: keyvitamin in controlling vascular calcification in chronic kidney disease. Kidney Int 2013; 83 : 782-4.
Brancaccio D, Biondi ML, Gallieni M, Turri O, Galassi A, Cecchini F, et al. Matrix gla protein gene polymorphisms : clinical correlates and cardiovascular mortality in chronic kidney disease patients. Am J Nephrol 2005; 25 : 548-52.
Crosier MD, Booth SL, Peter I, Dawson-Hughes B, Price PA, O'Donnell CJ, et al. Matrix gla protein polymorphisms are associated with coronary artery calcification in men. J Nutr Sci Vitaminol (Tokyo) 2009; 55 : 59-65.
Herrmann SM, Whatling C, Brand E, Nicaud V, Gariepy J, Simon A, et al. Polymorphisms of the human matrix gla protein (mgp) gene, vascular calcification, and myocardial infarction. Arterioscler Thromb Vasc Biol 2000; 20 : 2386-93.
Yoshikawa K, Abe H, Tominaga T, Nakamura M, Kishi S, Matsuura M, et al. 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 : 882-9.
Cassidy-Bushrow AE, Bielak LF, Levin AM, Sheedy 2nd. PF, Turner ST, Boerwinkle E, et al. Matrix gla protein gene polymorphism is associated with increased coronary artery calcification progression. Arterioscler Thromb Vasc Biol 2013; 33 : 645-51.
Wang Y, Chen J, Zhang Y, Yu W, Zhang C, Gong L, et al. Common genetic variants of mgp are associated with calcification on the arterial wall but not with calcification present in the atherosclerotic plaques. Circ Cardiovasc Genet 2013; 6 : 271-8.
Shroff R, Long DA, Shanahan C. Mechanistic insights into vascular calcification in ckd. J Am Soc Nephrol 2013; 24 : 179-89.
Boxma PY, van den Berg E, Geleijnse JM, Laverman GD, Schurgers LJ, Vermeer C, et al. Vitamin K intake and plasma desphosphouncarboxylated matrix gla-protein levels in kidney transplant recipients. PLoS One 2013; 7 : e47991.
Delanaye P, Krzesinski JM, Warling X, Moonen M, Smelten N, Medart L, et al. Dephosphorylated-uncarboxylated matrix gla protein concentration is predictive of vitamin K status and is correlated with vascular calcification in a cohort of hemodialysis patients. BMC Nephrol 2014; 15 : 145.
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 : 568-75.
Fusaro M, Crepaldi G, Maggi S, Galli F, D'Angelo A, Calo 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 : 317-23.
Shroff RC, Shah V, Hiorns MP, Schoppet M, Hofbauer LC, Hawa G, et al. The circulating calcification inhibitors, fetuin-a and osteoprotegerin, but not matrix gla protein, are associated with vascular stiffness and calcification in children on dialysis. Nephrol Dial Transplant 2008; 23 : 3263-71.
Hermans MM, Vermeer C, Kooman JP, Brandenburg V, Ketteler M, Gladziwa U, et al. Undercarboxylated matrix gla protein levels are decreased in dialysis patients and related to parameters of calcium-phosphate metabolism and aortic augmentation index. Blood Purif 2007; 25 : 395-401.
Krueger T, Schlieper G, Schurgers L, Cornelis T, Cozzolino M, Jacobi J, et al. Vitamin K1 to slow vascular calcification in haemodialysis patients (vitavask trial) : a rationale and study protocol. Nephrol Dial Transplant 2014; 29 : 1633-8.
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