Inflammatory, metabolic, and genetic mechanisms of vascular calcification

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 34, Issue 4, 2014, Pages 715-723

  Demer, Linda L ^a   Tintut, Yin ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

aortic valve; arteries; heterotopic ossification; vascular calcification

Indexed keywords

4 CARBOXYGLUTAMIC ACID; ADENOSINE; ALKALINE PHOSPHATASE; ELASTIN; FIBRILLIN; FIBROBLAST GROWTH FACTOR 23; FISH OIL; OSTEOPROTEGERIN; PHOSPHATE; PRELAMIN A; PROTEIN; PROTEIN GLUTAMINE GAMMA GLUTAMYLTRANSFERASE; PROTEIN GLUTAMINE GAMMA GLUTAMYLTRANSFERASE 2; PYROPHOSPHATE; UNCLASSIFIED DRUG; VITAMIN K GROUP; WARFARIN;

ABCC6 GENE; ADVERSE OUTCOME; APOPTOSIS; ARTERIAL STIFFNESS; ARTERY CALCIFICATION; ARTICLE; AUTOPHAGY; BIOMINERALIZATION; BLOOD VESSEL CALCIFICATION; BLOOD VESSEL COMPLIANCE; BONE DEVELOPMENT; BONE MINERALIZATION; CARDIOVASCULAR MORTALITY; CHONDROGENESIS; DIABETES MELLITUS; DISEASE ASSOCIATION; DISEASE CLASSIFICATION; DNA DAMAGE; ENCHONDRAL OSSIFICATION; ENPP1 GENE; GENE; HUMAN; HYPERLIPIDEMIA; INFLAMMATION; LIPID OXIDATION; MOLECULAR MECHANICS; MORBIDITY; NONHUMAN; OSSIFICATION; OSTEOPOROSIS; OSTEOPROGENITOR CELL; PHENOTYPE; PRIORITY JOURNAL; PROTEIN TRANSPORT; PSEUDOXANTHOMA ELASTICUM; VASCULAR DISEASE;

AORTIC VALVE; ARTERIES; HETEROTOPIC OSSIFICATION; VASCULAR CALCIFICATION;

ANIMALS; BLOOD VESSELS; CALCIFICATION, PHYSIOLOGIC; GENETIC PREDISPOSITION TO DISEASE; HUMANS; INFLAMMATION; INFLAMMATION MEDIATORS; PHENOTYPE; RISK FACTORS; VASCULAR CALCIFICATION;

EID: 84897066485     PISSN: 10795642     EISSN: 15244636     Source Type: Journal    
DOI: 10.1161/ATVBAHA.113.302070     Document Type: Article

References (85)

1. Demer LL. Effect of calcifcation on in vivo mechanical response of rabbit arteries to balloon dilation. Circulation. 1991;83:2083-2093.
2. Hoshino T, Chow LA, Hsu JJ, Perlowski AA, Abedin M, Tobis J, Tintut Y, Mal AK, Klug WS, Demer LL. Mechanical stress analysis of a rigid inclusion in distensible material: a model of atherosclerotic cal-cifcation and plaque vulnerability. Am J Physiol Heart Circ Physiol. 2009;297:H802-H810.
3. Kelly-Arnold A, Maldonado N, Laudier D, Aikawa E, Cardoso L, Weinbaum S. Revised microcalcifcation hypothesis for fbrous cap rupture in human coronary arteries. Proc Natl Acad Sci USA. 2013;110:10741-10746.
4. Qiao JH, Mertens RB, Fishbein MC, Geller SA. Cartilaginous metaplasia in calcifed diabetic peripheral vascular disease: morphologic evidence of enchondral ossifcation. Hum Pathol. 2003;34:402-407.
5. Schiller AL, Teitelbaum SL. Bones and joints. In: Rubin E, Farber, John L, eds. Pathology. Philadelphia, PA: Lippincott-Raven; 1999:1337-1347.
6. Proudfoot D, Skepper JN, Hegyi L, Bennett MR, Shanahan CM, Weissberg PL. Apoptosis regulates human vascular calcifcation in vitro: evidence for initiation of vascular calcifcation by apoptotic bodies. Circ Res. 2000;87:1055-1062.
7. Anderson HC. Mineralization by matrix vesicles. Scan Electron Microsc. 1984:II;953-964.
8. Kapustin AN, Davies JD, Reynolds JL, McNair R, Jones GT, Sidibe A, Schurgers LJ, Skepper JN, Proudfoot D, Mayr M, Shanahan CM. Calcium regulates key components of vascular smooth muscle cell-derived matrix vesicles to enhance mineralization. Circ Res. 2011;109:e1-12.
9. Chen NX, O'Neill KD, Chen X, Moe SM. Annexin-mediated matrix vesicle calcifcation in vascular smooth muscle cells. J Bone Miner Res. 2008;23:1798-1805.
10. New SE, Goettsch C, Aikawa M, Marchini JF, Shibasaki M, Yabusaki K, Libby P, Shanahan CM, Croce K, Aikawa E. Macrophage-derived matrix vesicles: an alternative novel mechanism for microcalcifcation in atherosclerotic plaques. Circ Res. 2013;113:72-77.
11. Sage AP, Lu J, Tintut Y, Demer LL. Hyperphosphatemia-induced nano-crystals upregulate the expression of bone morphogenetic protein-2 and osteopontin genes in mouse smooth muscle cells in vitro. Kidney Int. 2011;79:414-422.
12. Ross MH, Pawlina W. Bone. In: Ross MH, Pawlina W. Histology: A Text and Atlas With Correlated Cell and Molecular Biology. Philadelphia, PA: Wolters Kluwer, Lippincott Williams & Wilkins; 2011:218-252.
13. Farhat GN, Cauley JA, Matthews KA, Newman AB, Johnston J, Mackey R, Edmundowicz D, Sutton-Tyrrell K. Volumetric BMD and vascular cal-cifcation in middle-Aged women: the Study of Women's Health Across the Nation. J Bone Miner Res. 2006;21:1839-1846.
14. Hak AE, Pols HA, van Hemert AM, Hofman A, Witteman JC. Progression of aortic calcifcation is associated with metacarpal bone loss during menopause: a population-based longitudinal study. Arterioscler Thromb Vasc Biol. 2000;20:1926-1931.
15. Kawai K, Maruno H, Watanabe Y, Hirohata K. Fat necrosis of osteocytes as a causative factor in idiopathic osteonecrosis in heritable hyperlipemic rabbits. Clin Orthop Relat Res. 1980:273-282.
16. Watanabe Y, Kawai K, Hirohata K. Histopathology of femoral head osteo-necrosis in rheumatoid arthritis: the relationship between steroid therapy and lipid degeneration in the osteocyte. Rheumatol Int. 1989;9:25-31.
17. Tintut Y, Morony S, Demer LL. Hyperlipidemia promotes osteoclastic potential of bone marrow cells ex vivo. Arterioscler Thromb Vasc Biol. 2004;24:e6-e10.
18. Schafer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J, Muller-Esterl W, Schinke T, Jahnen-Dechent W. The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcifcation. J Clin Invest. 2003;112:357-366.
19. Aikawa E, Nahrendorf M, Figueiredo JL, Swirski FK, Shtatland T, Kohler RH, Jaffer FA, Aikawa M, Weissleder R. Osteogenesis associates with infammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation. 2007;116:2841-2850.
20. Abdelbaky A, Corsini E, Figueroa AL, Fontanez S, Subramanian S, Ferencik M, Brady TJ, Hoffmann U, Tawakol A. Focal arterial infamma-tion precedes subsequent calcifcation in the same location: a longitudinal FDG-PET/CT study. Circ Cardiovasc Imaging. 2013;6:747-754.
21. Abedin M, Lim J, Tang TB, Park D, Demer LL, Tintut Y. N-3 fatty acids inhibit vascular calcifcation via the p38-mitogen-Activated protein kinase and peroxisome proliferator-Activated receptor-gamma pathways. Circ Res. 2006;98:727-729.
22. Kageyama A, Matsui H, Ohta M, Sambuichi K, Kawano H, Notsu T, Imada K, Yokoyama T, Kurabayashi M. Palmitic acid induces osteoblastic differentiation in vascular smooth muscle cells through ACSL3 and NF-κB, novel targets of eicosapentaenoic acid. PLoS One. 2013;8:e68197.
23. Sun Y, Byon CH, Yuan K, Chen J, Mao X, Heath JM, Javed A, Zhang K, Anderson PG, Chen Y. Smooth muscle cell-specifc runx2 defciency inhibits vascular calcifcation. Circ Res. 2012;111:543-552.
24. Hessle L, Johnson KA, Anderson HC, Narisawa S, Sali A, Goding JW, Terkeltaub R, Millan JL. Tissue-nonspecifc alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proc Natl Acad Sci USA. 2002;99:9445-9449.
25. Yadav MC, Simão AM, Narisawa S, Huesa C, McKee MD, Farquharson C, Millán JL. Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1 and alkaline phosphatase function: a unifed model of the mechanisms of initiation of skeletal calcifcation. J Bone Miner Res. 2011;26:286-297.
26. Kiffer-Moreira T, Yadav MC, Zhu D, Narisawa S, Sheen C, Stec B, Cosford ND, Dahl R, Farquharson C, Hoylaerts MF, Macrae VE, Millán JL. Pharmacological inhibition of PHOSPHO1 suppresses vascular smooth muscle cell calcifcation. J Bone Miner Res. 2013;28:81-91.
27. Tang Z, Wang A, Yuan F, Yan Z, Liu B, Chu JS, Helms JA, Li S. Differentiation of multipotent vascular stem cells contributes to vascular diseases. Nat Commun. 2012;3:875.
28. Nguyen AT, Gomez D, Bell RD, et al. Smooth muscle cell plasticity: fact or fction? Circ Res. 2013;112:17-22.
29. Tang Z, Wang A, Wang D, Li S. Smooth muscle cells: to be or not to be? Response to Nguyen et Al. Circ Res. 2013;112:23-26.
30. Wong MN, Nguyen TP, Chen TH, Hsu JJ, Zeng X, Saw A, Demer EM, Zhao X, Tintut Y, Demer LL. Preferred mitotic orientation in pattern formation by vascular mesenchymal cells. Am J Physiol Heart Circ Physiol. 2012;303:H1411-H1417.
31. Chen TH, Hsu JJ, Zhao X, Guo C, Wong MN, Huang Y, Li Z, Garfnkel A, Ho CM, Tintut Y, Demer LL. Left-right symmetry breaking in tissue morphogenesis via cytoskeletal mechanics. Circ Res. 2012;110:551-559.
32. Cheng SL, Shao JS, Behrmann A, Krchma K, Towler DA. Dkk1 and MSX2-Wnt7b signaling reciprocally regulate the endothelial-mesenchymal transition in aortic endothelial cells. Arterioscler Thromb Vasc Biol. 2013;33:1679-1689.
33. Yao Y, Jumabay M, Ly A, Radparvar M, Cubberly MR, Boström KI. A role for the endothelium in vascular calcifcation. Circ Res. 2013;113:495-504.
34. Yang S, Eto H, Kato H, Doi K, Kuno S, Kinoshita K, Ma H, Tsai CH, Chou WT, Yoshimura K. Comparative characterization of stromal vascular cells derived from three types of vascular wall and adipose tissue. Tissue Eng Part A. 2013;19:2724-2734.
35. Ueland T, Dahl CP, Gullestad L, Aakhus S, Broch K, Skårdal R, Vermeer C, Aukrust P, Schurgers LJ. Circulating levels of non-phos-phorylated undercarboxylated matrix Gla protein are associated with disease severity in patients with chronic heart failure. Clin Sci (Lond). 2011;121:119-127.
36. Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G. Spontaneous calcifcation of arteries and cartilage in mice lacking matrix GLA protein. Nature. 1997;386:78-81.
37. Boström 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;276:14044-14052.
38. Wallin R, Cain D, Hutson SM, Sane DC, Loeser R. Modulation of the binding of matrix Gla protein (MGP) to bone morphogenetic protein-2 (BMP-2). Thromb Haemost. 2000;84:1039-1044.
39. Khavandgar Z, Roman H, Li J, Lee S, Vali H, Brinckmann J, Davis EC, Murshed M. Elastin haploinsuffciency impedes the progression of arterial calcifcation in MGP-defcient mice. J Bone Miner Res. 2014;29:327-337.
40. Schurgers LJ, Joosen IA, Laufer EM, et al. Vitamin K-Antagonists accelerate atherosclerotic calcifcation and induce a vulnerable plaque phenotype. PLoS One. 2012;7:e43229.
41. Shea MK, Booth SL, Miller ME, Burke GL, Chen H, Cushman M, Tracy RP, Kritchevsky SB. Association between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the MultiEthnic Study of Atherosclerosis. Am J Clin Nutr. 2013;98:197-208.
42. 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. 2012;7:e47991.
43. McCabe KM, Booth SL, Fu X, Shobeiri N, Pang JJ, Adams MA, Holden RM. Dietary vitamin K and therapeutic warfarin alter the susceptibility to vascular calcifcation in experimental chronic kidney disease. Kidney Int. 2013;83:835-844.
44. Furie B, Bouchard BA, Furie BC. Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid. Blood. 1999;93:1798-1808.
45. Krüger T, Oelenberg S, Kaesler N, Schurgers LJ, van de Sandt AM, Boor P, Schlieper G, Brandenburg VM, Fekete BC, Veulemans V, Ketteler M, Vermeer C, Jahnen-Dechent W, Floege J, Westenfeld R. Warfarin induces cardiovascular damage in mice. Arterioscler Thromb Vasc Biol. 2013;33:2618-2624.
46. Nurminskaya M, Kaartinen MT. Transglutaminases in mineralized tissues. Front Biosci. 2006;11:1591-1606.
47. Vyavahare NR, Hirsch D, Lerner E, Baskin JZ, Zand R, Schoen FJ, Levy RJ. Prevention of calcifcation of glutaraldehyde-crosslinked porcine aortic cusps by ethanol preincubation: mechanistic studies of protein structure and water-biomaterial relationships. J Biomed Mater Res. 1998;40:577-585.
48. Johnson KA, Polewski M, Terkeltaub RA. Transglutaminase 2 is central to induction of the arterial calcifcation program by smooth muscle cells. Circ Res. 2008;102:529-537.
49. Beazley KE, Banyard D, Lima F, Deasey SC, Nurminsky DI, Konoplyannikov M, Nurminskaya MV. Transglutaminase inhibitors attenuate vascular calcifcation in a preclinical model. Arterioscler Thromb Vasc Biol. 2013;33:43-51.
50. Beazley KE, Eghtesad S, Nurminskaya MV. Quercetin attenuates warfarin-induced vascular calcifcation in vitro independently from matrix Gla protein. J Biol Chem. 2013;288:2632-2640.
51. Chen NX, O'Neill K, Chen X, Kiattisunthorn K, Gattone VH, Moe SM. Transglutaminase 2 accelerates vascular calcifcation in chronic kidney disease. Am J Nephrol. 2013;37:191-198.
52. Li Q, Jiang Q, Uitto J. Ectopic mineralization disorders of the extracellular matrix of connective tissue: molecular genetics and pathomecha-nisms of aberrant calcifcation [published online ahead of print July 25, 2013]. Matrix Biol. doi: 10.1016/j.matbio.2013.06.003: http://dx.doi. org/10.1016/j.matbio.2013.06.003. Accessed February 7, 2014.
53. Pomozi V, Le Saux O, Brampton C, Apana A, Iliás A, Szeri F, Martin L, Monostory K, Paku S, Sarkadi B, Szakács G, Váradi A. ABCC6 is a baso-lateral plasma membrane protein. Circ Res. 2013;112:e148-e151.
54. Martin LJ, Lau E, Singh H, et al. ABCC6 localizes to the mitochondria-Associated membrane. Circ Res. 2012;111:516-520.
55. Jiang Q, Endo M, Dibra F, Wang K, Uitto J. Pseudoxanthoma elasticum is a metabolic disease. J Invest Dermatol. 2009;129:348-354.
56. Borst P, van de Wetering K, Schlingemann R. Does the absence of ABCC6 (multidrug resistance protein 6) in patients with Pseudoxanthoma elasti-cum prevent the liver from providing suffcient vitamin K to the periphery? Cell Cycle. 2008;7:1575-1579.
57. Wang J, Near S, Young K, Connelly PW, Hegele RA. ABCC6 gene polymorphism associated with variation in plasma lipoproteins. J Hum Genet. 2001;46:699-705.
58. Jiang Q, Li Q, Grand-Pierre AE, Schurgers LJ, Uitto J. Administration of vitamin K does not counteract the ectopic mineralization of connective tissues in Abcc6 (-/-) mice, a model for pseudoxanthoma elasticum. Cell Cycle. 2011;10:701-707.
59. Gorgels TG, Waarsing JH, Herfs M, Versteeg D, Schoensiegel F, Sato T, Schlingemann RO, Ivandic B, Vermeer C, Schurgers LJ, Bergen AA. Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcifcation in a mouse model for pseudoxanthoma elasticum. J Mol Med (Berl). 2011;89:1125-1135.
60. Nitschke Y, Baujat G, Botschen U, et al. Generalized arterial calcifcation of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. Am J Hum Genet. 2012;90:25-39.
61. Byon CH, Sun Y, Chen J, Yuan K, Mao X, Heath JM, Anderson PG, Tintut Y, Demer LL, Wang D, Chen Y. Runx2-upregulated receptor activator of nuclear factor κB ligand in calcifying smooth muscle cells promotes migration and osteoclastic differentiation of macrophages. Arterioscler Thromb Vasc Biol. 2011;31:1387-1396.
62. Mazière C, Salle V, Gomila C, Mazière JC. Oxidized low density lipoprotein enhanced RANKL expression in human osteoblast-like cells. Involvement of ERK, NFkappaB and NFAT. Biochim Biophys Acta. 2013;1832:1756-1764.
63. Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS. osteoprotegerin-defcient mice develop early onset osteoporosis and arterial calcifcation. Genes Dev. 1998;12:1260-1268.
64. Morony S, Tintut Y, Zhang Z, Cattley RC, Van G, Dwyer D, Stolina M, Kostenuik PJ, Demer LL. Osteoprotegerin inhibits vascular calcifcation without affecting atherosclerosis in ldlr(-/-) mice. Circulation. 2008;117:411-420.
65. Zhou S, Fang X, Xin H, Li W, Qiu H, Guan S. Osteoprotegerin inhibits calcifcation of vascular smooth muscle cell via down regulation of the Notch1-RBP-Jκ/Msx2 signaling pathway. PLoS One. 2013;8:e68987.
66. Callegari A, Coons ML, Ricks JL, Yang HL, Gross TS, Huber P, Rosenfeld ME, Scatena M. Bone marrow-or vessel wall-derived osteoprotegerin is suffcient to reduce atherosclerotic lesion size and vascular calcifcation. Arterioscler Thromb Vasc Biol. 2013;33:2491-2500.
67. Osako MK, Nakagami H, Shimamura M, Koriyama H, Nakagami F, Shimizu H, Miyake T, Yoshizumi M, Rakugi H, Morishita R. Cross-talk of receptor activator of nuclear factor-κB ligand signaling with renin-Angiotensin system in vascular calcifcation. Arterioscler Thromb Vasc Biol. 2013;33:1287-1296.
68. Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997;390:45-51.
69. Hu MC, Shi M, Zhang J, Quiñones H, Griffth C, Kuro-o M, Moe OW. Klotho defciency causes vascular calcifcation in chronic kidney disease. J Am Soc Nephrol. 2011;22:124-136.
70. Lim K, Lu TS, Molostvov G, Lee C, Lam FT, Zehnder D, Hsiao LL. Vascular Klotho defciency potentiates the development of human artery calcifcation and mediates resistance to fbroblast growth factor 23. Circulation. 2012;125:2243-2255.
71. Scialla JJ, Lau WL, Reilly MP, et al; Chronic Renal Insuffciency Cohort Study Investigators. Fibroblast growth factor 23 is not associated with and does not induce arterial calcifcation. Kidney Int. 2013;83:1159-1168.
72. Xiao Y, Peng C, Huang W, Zhang J, Xia M, Zhang Y, Ling W. Circulating fbroblast growth factor 23 is associated with angiographic severity and extent of coronary artery disease. PLoS One. 2013;8:e72545.
73. Everhart JE, Pettitt DJ, Knowler WC, Rose FA, Bennett PH. Medial arterial calcifcation and its association with mortality and complications of diabetes. Diabetologia. 1988;31:16-23.
74. Menini S, Iacobini C, Ricci C, Blasetti Fantauzzi C, Salvi L, Pesce CM, Relucenti M, Familiari G, Taurino M, Pugliese G. The galectin-3/RAGE dyad modulates vascular osteogenesis in atherosclerosis. Cardiovasc Res. 2013;100:472-480.
75. Nguyen N, Naik V, Speer MY. Diabetes mellitus accelerates cartilaginous metaplasia and calcifcation in atherosclerotic vessels of LDLr mutant mice. Cardiovasc Pathol. 2013;22:167-175.
76. Kim HS, Chung W, Kim AJ, Ro H, Chang JH, Lee HH, Jung JY. Circulating levels of soluble receptor for advanced glycation end product are inversely associated with vascular calcifcation in patients on hemodialysis independent of S100A12 levels. Nephrology (Carlton). 2013;12:777-782.
77. Hofmann Bowman MA, Gawdzik J, Bukhari U, Husain AN, Toth PT, Kim G, Earley J, McNally EM. S100A12 in vascular smooth muscle accelerates vascular calcifcation in apolipoprotein E-null mice by activating an osteogenic gene regulatory program. Arterioscler Thromb Vasc Biol. 2011;31:337-344.
78. Fadini GP, Albiero M, Menegazzo L, Boscaro E, Agostini C, de Kreutzenberg SV, Rattazzi M, Avogaro A. Procalcifc phenotypic drift of circulating progenitor cells in type 2 diabetes with coronary artery disease. Exp Diabetes Res. 2012;2012:921685.
79. Flammer AJ, Gössl M, Li J, Matsuo Y, Reriani M, Loeffer D, Simari RD, Lerman LO, Khosla S, Lerman A. Patients with an HbA1c in the pre-diabetic and diabetic range have higher numbers of circulating cells with osteogenic and endothelial progenitor cell markers. J Clin Endocrinol Metab. 2012;97:4761-4768.
80. Doyon M, Mathieu P, Moreau P. Decreased expression of γ-carboxylase in diabetes-Associated arterial stiffness: impact on matrix Gla protein. Cardiovasc Res. 2013;97:331-338.
81. Sinha A, Vyavahare NR. High-glucose levels and elastin degradation products accelerate osteogenesis in vascular smooth muscle cells. Diab Vasc Dis Res. 2013;10:410-419.
82. Saremi A, Bahn G, Reaven PD; VADT Investigators. Progression of vascular calcifcation is increased with statin use in the Veterans Affairs Diabetes Trial (VADT). Diabetes Care. 2012;35:2390-2392.
83. Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, Boyce B, Zhao M, Gutierrez G. Stimulation of bone formation in vitro and in rodents by statins. Science. 1999;286:1946-1949.
84. Liu Y, Drozdov I, Shroff R, Beltran LE, Shanahan CM. Prelamin A accelerates vascular calcifcation via activation of the DNA damage response and senescence-Associated secretory phenotype in vascular smooth muscle cells. Circ Res. 2013;112:e99-e109.
85. Dai XY, Zhao MM, Cai Y, Guan QC, Zhao Y, Guan Y, Kong W, Zhu WG, Xu MJ, Wang X. Phosphate-induced autophagy counteracts vascular calcif-cation by reducing matrix vesicle release. Kidney Int. 2013;83:1042-1051.