Bone Remodeling Biomarkers: New Actors on the Old Cardiovascular Stage

Biomarker Validation: Technological, Clinical and Commercial Aspects

Volumn , Issue , 2015, Pages 107-146

  Vassalle, Cristina ^a   Maffei, Silvia ^a   Iervasi, Giorgio ^a  

^a INSTITUTE OF CLINICAL PHYSIOLOGY   (Italy)

Author keywords

Bone remodeling biomarkers; Cardiovascular disease (CVD); Impaired mineral metabolism; Osteoporosis; Pathophysiological mechanisms

Indexed keywords

BIOMARKERS; BIOMINERALIZATION; CARDIOLOGY; DISEASES; METABOLISM; PHOSPHATASES; PHYSIOLOGY;

BIOCHEMICAL MARKERS; BONE REMODELING; CARDIOVASCULAR DISEASE; OSTEOPOROSIS; PATHOPHYSIOLOGICAL; PROTEOLYTIC ACTIVITIES; TARTRATE-RESISTANT ACID PHOSPHATASE; VASCULAR CALCIFICATION;

BONE;

EID: 85016088589     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9783527680658.ch7     Document Type: Chapter

References (286)

1. Eastell, R., Newman, C., and Crossman, D.C. (2010) Cardiovascular disease and bone. Arch. Biochem. Biophys., 503, 78-83.
2. Vassalle, C., Simoncini, T., Chedraui, P., and Pérez-López, F.R. (2012) Why sex matters: the biological mechanisms of cardiovascular disease. Gynecol. Endocrinol., 28, 746-751.
3. Baggio, G., Corsini, A., Floreani, A., Giannini, S., and Zagonel, V. (2013) Gender medicine: a task for the third millennium. Clin. Chem. Lab. Med., 51, 713-727.
4. Zhang, Y., Zhou, P., and Kimondo, J.W. (2012) Adiponectin and osteocalcin: relation to insulin sensitivity. Biochem. Cell Biol., 90, 613-620.
5. Banack, H.R. and Kaufman, J.S. (2014) The obesity paradox: understanding the effect of obesity on mortality among individuals with cardiovascular disease. Prev. Med., 10. doi: 10.1016/j.ypmed.2014.02.003.
6. De Laet, C., Kanis, J.A., Odén, A., Johanson, H., Johnell, O., Delmas, P., Eisman, J.A., Kroger, H., Fujiwara, S., Garnero, P., McCloskey, E.V., Mellstrom, D., Melton, L.J. III, Meunier, P.J., Pols, H.A., Reeve, J., Silman, A., and Tenenhouse, A. (2005) Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos. Int., 16, 1330-1338.
7. Nakamura, K., Fuster, J.J., and Walsh, K. (2013) Adipokines: a link between obesity and cardiovascular disease. J. Cardiol., 16. doi: 10.1016/j.jjcc.2013.11.006.
8. Matsuzawa, Y. (2005) Adiponectin: Identification, physiology and clinical relevance in metabolic and vascular disease. Atheroscler. Suppl., 6, 7-14.
9. Ong, T., Sahota, O., Tan, W., and Marshall, L. (2014) A United Kingdom perspective on the relationship between body mass index (BMI) and bone health: a cross sectional analysis of data from the Nottingham Fracture Liaison Service. Bone, 59, 207-210.
10. Gourdy, P., Calippe, B., Laurell, H., Trémollières, F., Douin-Echinard, V., Lenfant, F., Bayard, F., Guery, J.C., and Arnal, J.F. (2008) Role of inflammatory cytokines in the effect of estradiol on atheroma. Clin. Exp. Pharmacol. Physiol., 35, 396-401.
11. De Benedetti, F., Rucci, N., Del Fattore, A., Peruzzi, B., Paro, R., Longo, M., Vivarelli, M., Muratori, F., Berni, S., Ballanti, P., and Teti, A. (2006) Impaired skeletal development in interleukin-6 transgenic mice. A model for the impact of chronic inflammation in growing skeletal system. Arthritis Rheum., 54, 3551-3563.
12. Schett, G. (2011) Effects of inflammatory and anti-inflammatory cytokines on the bone. Eur. J. Clin. Invest., 41, 1361-1366.
13. Papanicolaou, D.A., Wilder, R.L., Manolagas, S.C., and Chrousos, G.P. (1998) The pathophysiologic roles of interleukin-6 in human disease. Ann. Intern. Med., 128, 127-137.
14. Bertolini, D.R., Nedwin, G.E., Bringman, T.S., Smith, D.D., and Mundy, G.R. (1986) Stimulation of bone resorption and inhibition of bone formation in vitro by human tumor necrosis factors. Nature, 319, 516-518.
15. Cauley, J.A., Danielson, M.E., Boudreau, R., Forrest, K.Y.Z., Zmuda, J.M., Pahor, M., Tylavsky, F., Cummings, S.R., Harris, T., and Newman, A.B. (2007) Inflammatory markers and incident fracture risk in older men and women: the health aging and body composition study. J. Bone Miner. Res., 22, 1088-1095.
16. Barbour, K.E., Boudreau, R., Danielson, M.E., Youk, A.O., Wactawski-Wende, J., Greep, N.C., LaCroix, A.Z., Jackson, R.D., Wallace, R.B., Bauer, D.C., Allison, M.A., and Cauley, J.A. (2012) Inflammatory markers and the risk of hip fracture: the Women's Health Initiative. J. Bone Miner. Res., 27, 1167-1176.
17. Koh, J.M., Khang, Y.H., Jung, C.H., Bae, S., Kim, D.J., Chung, Y.E., and Kim, G.S. (2005) Higher circulating hsCRP levels are associated with lower bone mineral density in healthy pre- and postmenopausal women: evidence for a link between systemic inflammation and osteoporosis. Osteoporos. Int., 16, 1263-1271.
18. Pasco, J.A., Kotowicz, M.A., Henry, M.J., Nicholson, G.C., Spilsbury, H.J., Box, J.D., and Schneider, H.G. (2006) High-sensitivity C-reactive protein and fracture risk in elderly women. J. Am. Med. Assoc., 20, 1353-1355.
19. Ishii, S., Cauley, J.A., Greendale, G.A., Crandall, C.J., Danielson, M.E., Ouchi, Y., and Karlamangla, A.S. (2013) Creactive protein, bone strength, and 9-year fracture risk: data from the study of women's health across the nation (SWAN). J. Bone Miner. Res., 28, 1688-1698.
20. de Pablo, P., Cooper, M.S., and Buckley, C.D. (2012) Association between bone mineral density and C-reactive protein in a large population-based sample. Arthritis Rheum., 64, 2624-2631.
21. Sponholtz, T.R., Zhang, X., Fontes, J.D., Meigs, J.B., Cupples, L.A., Kiel, D.P., Hannan, M.T., and McLean, R.R. (2013) Association between inflammatory biomarkers and bone mineral density in a community-based cohort of men and women: the Framingham Osteoporosis Study. Arthritis Care Res. (Hoboken), (66.):1233-40.
22. Ding, C., Parameswaran, V., Udayan, R., Burgess, J., and Jones, G. (2008) Circulating levels of inflammatory markers predict change in bone mineral density and resorption in older adults: a longitudinal study. J. Clin. Endocrinol. Metab., 93, 1952-1958.
23. Ahmadi-Abhari, S., Luben, R.N., Wareham, N.J., and Khaw, K.T. (2013) C-reactive protein and fracture risk: European prospective investigation into Cancer Norfolk Study. Bone, 56, 67-72.
24. Vassalle, C., Petrozzi, L., Botto, N., Andreassi, M.G., and Zucchelli, G.C. (2004) Oxidative stress and its association with coronary artery disease and different atherogenic risk factors. J. Intern. Med., 256, 308-315.
25. Vassalle, C., Bianchi, S., Battaglia, D., Landi, P., Bianchi, F., and Carpeggiani, C. (2012) Elevated levels of oxidative stress as a prognostic predictor of major adverse cardiovascular events in patients with coronary artery disease. J. Atheroscler. Thromb., 19, 712-717.
26. Wang, K., Niu, J., Kim, H., and Kolattukudy, P.E. (2011) Osteoclast precursor differentiation by MCPIP via oxidative stress, endoplasmic reticulum stress, and autophagy. J. Mol. Cell Biol., 3, 360-368.
27. Suh, K.S., Choi, E.M., Rhee, S.Y., and Kim, Y.S. (2014) Methylglyoxal induces oxidative stress and mitochondrial dysfunction in osteoblastic MC3T3-E1 cells. Free Radic. Res., 48, 206-217.
28. Cervellati, C., Bonaccorsi, G., Cremonini, E., Romani, A., Fila, E., Castaldini, M.C., Ferrazzini, S., Giganti, M., and Massari, L. (2014) Oxidative stress and bone resorption interplay as a possible trigger for postmenopausal osteoporosis. Biomed. Res. Int., 2014;2014:569563. doi: 10.1155/2014/569563. 1-8.
29. Rahnert, J., Fan, X., Case, N., Murphy, T.C., Grassi, F., Sen, B., and Rubin, J. (2008) The role of nitric oxide in the mechanical repression of RANKL in bone stromal cells. Bone, 43, 48-54.
30. Zheng, H., Yu, X., Collin-Osdoby, P., and Osdoby, P. (2006) RANKL stimulates inducible nitric-oxide synthase expression and nitric oxide production in developing osteoclasts. An autocrine negative feedback mechanism triggered by RANKL-induced interferon-beta via NF-kappaB that restrains osteoclastogenesis and bone resorption. J. Biol. Chem., 281, 15809-15820.
31. Kazakov, A., Müller, P., Jagoda, P., Semenov, A., Böhm, M., and Laufs, U. (2012) Endothelial nitric oxide synthase of the bone marrow regulates myocardial hypertrophy, fibrosis, and angiogenesis. Cardiovasc. Res., 93, 397-405.
32. Wald, D.S., Law, M., and Morris, J.K. (2002) Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ, 325, 1202.
33. Homocysteine Studies Collaboration (2002) Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. J. Am. Med. Assoc., 288, 2015-2022.
34. Vacek, T.P., Kalani, A., Voor, M.J., Tyagi, S.C., and Tyagi, N. (2013) The role of homocysteine in bone remodeling. Clin. Chem. Lab. Med., 51, 579-590.
35. McFarlane, S.I., Muniyappa, R., Shin, J.J., Bahtiyar, G., and Sowers, J.R. (2004) Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link? Endocrine, 23, 1-10.
36. Zhu, K., Beilby, J., Dick, I.M., Devine, A., Soós, M., and Prince, R.L. (2009) The effects of homocysteine and MTHFR genotype on hip bone loss and fracture risk in elderly women. Osteoporos. Int., 20, 1183-1191.
37. Urano, T., Shiraki, M., Saito, M., Sasaki, N., Ouchi, Y., and Inoue, S. (2013) Polymorphism of SLC25A32, the folate transporter gene, is associated with plasma folate levels and bone fractures in Japanese postmenopausal women. Geriatr. Gerontol. Int. doi: 10.1111/ggi.12201.
38. Kuroda, T., Tanaka, S., Saito, M., Shiraki, Y., and Shiraki, M. (2013) Plasma level of homocysteine associated with severe vertebral fracture in postmenopausal women. Calcif. Tissue Int., 93, 269-275.
39. Leboff, M.S., Narweker, R., LaCroix, A., Wu, L., Jackson, R., Lee, J., Bauer, D.C., Cauley, J., Kooperberg, C., Lewis, C., Thomas, A.M., and Cummings, S. (2009) Homocysteine levels and risk of hip fracture in postmenopausal women. J. Clin. Endocrinol. Metab., 94, 1207-1213.
40. El Maghraoui, A., Ghozlani, I., Mounach, A., Rezqi, A., Oumghar, K., Achemlal, L., Bezza, A., and Ouzzif, Z. (2012) Homocysteine, folate, and vitamin B12 levels and vertebral fracture risk in postmenopausal women. J. Clin. Densitom., 15, 328-333.
41. Périer, M.A., Gineyts, E., Munoz, F., Sornay-Rendu, E., and Delmas, P.D. (2007) Homocysteine and fracture risk in postmenopausal women: the OFELY study. Osteoporos. Int., 18, 1329-1336.
42. Claes, L., Schmalenbach, J., Herrmann, M., Olkü, I., Garcia, P., Histing, T., Obeid, R., Schorr, H., Herrmann, W., Pohlemann, T., Menger, M.D., and Holstein, J.H. (2009) Hyperhomocysteinemia is associated with impaired fracture healing in mice. Calcif. Tissue Int., 85, 17-21.
43. Miyao, M., Morita, H., Hosoi, T., Kurihara, H., Inoue, S., Hoshino, S., Shiraki, M., Yazaki, Y., and Ouchi, Y. (2000) Association of methylenetetrahydrofolate reductase (MTHFR) polymorphism with bone mineral density in postmenopausal Japanese women. Calcif. Tissue Int., 66, 190-194.
44. Anagnostis, P., Karagiannis, A., Kakafika, A.I., Tziomalos, K., Athyros, V.G., and Mikhailidis, D.P. (2009) Atherosclerosis and osteoporosis: agedependent degenerative processes or related entities? Osteoporos. Int., 20, 197-207.
45. Bostrom, K. (2001) Insights into the mechanism of vascular calcification. Am. J. Cardiol., 88, 20e-22e.
46. Bostrom, K. and Demer, L.L. (2000) Regulatory mechanisms in vascular calcification. Crit. Rev. Eukaryot. Gene Expr., 10, 151-158.
47. Dhore, C.R., Cleutjens, J.P., Lutgens, E., Cleutjens, K.B., Geusens, P.P., Kitslaar, P.J., Tordoir, J.H., Spronk, H.M., Vermeer, C., and Daemen, M.J. (2001) Differential expression of bone matrix regulatory, proteins in human atheroesclerotic plaques. Arterioscler. Thromb. Vasc. Biol., 21, 1998-2003.
48. Parhami, F., Morrow, A.D., Balucan, J., Leitinger, N., Watson, A.D., Tintut, Y., Berliner, J.A., and Demer, L.L. (1997) Lipid oxidation products have opposite effects on calcifying vascular cell and bone cell differentiation. A possible explanation for the paradox of arterial calcification in osteoporotic patients. Arterioscler. Thromb. Vasc. Biol., 17, 680-687.
49. Tintut, Y. and Demer, L. (2006) Role of osteoprotegerin and its ligands and competing receptors in atherosclerotic calcification. J. Investig. Med., 54, 395-401.
50. Mazière, C., Salle, V., Gomila, C., and Mazière, J.C. (2013) Oxidized low density lipoprotein enhanced RANKL expression in human osteoblast-like cells. Involvement of ERK,NFkappaB and NFAT. Biochim. Biophys. Acta, 1832, 1756-1764.
51. Almeida, M., Ambrogini, E., Han, L., Manolagas, S.C., and Jilka, R.L. (2009) Increased lipid oxidation causes oxidative stress, increased peroxisome poliferator-activated receptor-gamma expression and diminished pro-osteogenic Wnt signaling in the skeleton. J. Biol. Chem., 284, 27438-27448.
52. Mazière, C., Salle, V., Gomila, C., and Mazière, J.C. (2013) Oxidized low density lipoprotein increases RANKL level in human vascular cells. Involvement of oxidative stress. Biochem. Biophys. Res. Commun., 440, 295-299.
53. Panizo, S., Cardus, A., Encinas, M., Parisi, E., Valcheva, P., López-Ongil, S., Coll, B., Fernandez, E., and Valdivielso, J.M. (2009) RANKL increases vascular smooth muscle cell calcification through a RANK-BMP4-dependent pathway. Circ. Res., 104, 1041-1048.
54. Parhami, F., Tintut, Y., Beamer, W.G., Gharavi, N., Goodman, W., and Demer, L.L. (2001) Atherogenic high-fat diet reduces bone mineralization in mice. J. Bone Miner. Res., 16, 182-188.
55. Pelton, K., Krieder, J., Joiner, D., Freeman, M.R., Goldstein, S.A., and Solomon, K.R. (2012) Hypercholesterolemia promotes an osteoporotic phenotype. Am. J. Pathol., 181, 928-936.
56. Jeong, I.K., Cho, S.W., Kim, S.W., Choi, H.J., Park, K.S., Kim, S.Y., Lee, H.K., Cho, S.H., Oh, B.H., and Shin, C.S. (2010) Lipid profiles and bone mineral density in pre- and postmenopausal women in Korea. Calcif. Tissue Int., 87, 507-512.
57. Orozco, P. (2004) Atherogenic lipid profile and elevated lipoprotein (a) are associated with lower bone mineral density in early postmenopausal overweight women. Eur. J. Epidemiol., 19, 1105-1112.
58. Samelson, E.J., Cupples, L.A., Hannan, M.T., Wilson, P.W., Williams, S.A., Vaccarino, V., Zhang, Y., and Kiel, D.P. (2004) Long-term effects of serum cholesterol on bone mineral density in women and men: the Framingham Osteoporosis study. Bone, 34, 557-561.
59. Solomon, D.H., Avorn, J., Canning, C.F., and Wang, P.S. (2005) Lipid levels and bone mineral density. Am. J. Med., 118, 1414.
60. Yamaguchi, T., Sugimoto, T., Yano, S., Yamauchi, M., Sowa, H., Chen, Q., and Chihara, K. (2002) Plasma lipids and osteoporosis in postmenopausal women. Endocr. J., 49, 211-217.
61. Adami, S., Braga, V., Zamboni, M., Gatti, D., Rossini, M., Bakri, J., and Battaglia, E. (2004) Relationship between lipids and bone mass in 2 cohorts of healthy women and men. Calcif. Tissue Int., 74, 136-142.
62. Meema, H.E. (1966) Menopausal and aging changes in muscle mass and bone mineral content. A roentgenographic study. J. Bone Joint Surg. Am., 48, 1138-1144.
63. Rosano, G.M., Maffei, S., Andreassi, M.G., Vitale, C., Vassalle, C., Gambacciani, M., Stramba-Badiale, M., and Mercuro, G. (2009) Hormone replacement therapy and cardioprotection: a new dawn? A statement of the Study Group on Cardiovascular Disease in Women of the Italian Society of Cardiology on hormone replacement therapy in postmenopausal women. J. Cardiovasc. Med. (Hagerstown), 10, 85-92.
64. Riggs, B.L. (2000) The mechanisms of estrogen regulation of bone resorption. J. Clin. Invest., 106, 1203-1204.
65. Stevenson, J.C., Panay, N., and Pexman-Fieth, C. (2013) Oral estradiol and dydrogesterone combination therapy in postmenopausal women: review of efficacy and safety. Maturitas, 76, 10-21.
66. Losordo, D.W., Kearney, M., Kim, E.A., Jekanowski, J., and Isner, J.M. (1994) Variable expression of the estrogen receptor in normal and atherosclerotic coronary arteries of premenopausal women. Circulation, 89, 1501-1510.
67. Clarkson, T.B. (2007) Estrogen effects on arteries vary with stage of reproductive life and extent of subclinical atherosclerosis progression. Menopause, 14, 373-384.
68. Barrett-Connor, E., Mueller, J.E., von Mühlen, D.G., Laughlin, G.A., Schneider, D.L., and Sartoris, D.J. (2000) Low levels of esrtadiol are associated with vertebral fractures in older men, but not women: the Rancho Bernardo Study. J. Clin. Endocrinol. Metab., 85, 219-223.
69. Doherty, T.M., Fitzpatrick, L.A., Inoue, D., Qiao, J.H., Fishbein, M.C., Detrano, R.C., Shah, P.K., and Rajavashisth, T.B. (2004) Molecular, endocrine, and genetic mechanisms of arterial calcification. Endocr. Rev., 25, 629-672.
70. Baldini V, Mastropasqua M, Francucci CM, D'Erasmo E. Cardiovascular disease and osteoporosis. J. Endocrinol. Invest. 2005; 28 (10 Suppl.):69-72.
71. Hak, A.E., Polderman, K.H., Westendorp, I.C., Jakobs, C., Hofman, A., Witteman, J.C., and Stehouwer, C.D. (2000) Increased plasma homocysteine after menopause. Atherosclerosis, 149, 163-168.
72. Zhu, X., Bonet, B., and Knopp, R.H. (2000) Estradiol 17beta inhibition of LDL oxidation and endothelian cell cytotoxicity is opposed by progestins to different degrees. Atherosclerosis, 148, 31-41.
73. Khosla, S., Atkinson, E.J., Melton, L.J. III, and Riggs, B.L. (1997) Effects of age and estrogen status on serum parathyroid hormone levels and biochemical markers of bone turnover in women: a population based study. J. Clin. Endocrinol. Metab., 82, 1522-1527.
74. Stefenelli, T., Mayr, H., Bergler-Klein, J., Globits, S., Woloszczuk, W., and Niederle, B. (1993) Primary hyperparathyroidism: incidence of cardiac abnormalities and partial reversibility after successful parathyroidectomy. Am. J. Med., 95, 197-202.
75. Sabatino, L., Picano, E., and Andreassi, M.G. (2012) Telomere shortening and ionizing radiation: a possible role in vascular dysfunction? Int. J. Radiat. Biol., 88, 830-839.
76. Pignolo, R.J., Suda, R.K., McMillan, E.A., Shen, J., Lee, S.H., Choi, Y., Wright, A.C., and Johnson, F.B. (2008) Defects in telomere maintenance molecules impair osteoblast differentiation and promote osteoporosis. Aging Cell, 7, 23-31.
77. Bakhireva, L.N., Barrett-Connor, E.L., Laughlin, G.A., and Kritz-Silverstein, D. (2005) Differences in association of bone mineral density with coronary artery calcification in men and women: the Rancho Bernardo Study. Menopause, 12, 691-698.
78. Manson, J.E., Allison, M.A., Rossouw, J.E., Carr, J.J., Langer, R.D., Hsia, J., Kuller, L.H., Cochrane, B.B., Hunt, J.R., Ludlam, S.E., Pettinger, M.B., Gass, M., Margolis, K.L., Nathan, L., Ockene, J.K., Prentice, R.L., Robbins, J., and Stefanick, M.L. (2007) Estrogen therapy and coronary-artery calcification. N. Engl. J. Med., 356, 2591-2602.
79. Osako, M.K., Nakagami, H., Koibuchi, N., Shimizu, H., Nakagami, F., Koriyama, H., Shimamura, M., Miyake, T., Rakugi, H., and Morishita, R. (2010) Estrogen inhibits vascular calcification via vascular RANKL system: common mechanism of osteoporosis and vascular calcification. Circ. Res., 107, 466-475.
80. Laurent, M., Gielen, E., Claessens, F., Boonen, S., and Vanderschueren, D. (2013) Osteoporosis in older men: recent advances in pathophysiology and treatment. Best Pract. Res. Clin. Endocrinol. Metab., 27, 527-539.
81. Spoletini, I., Caprio, M., Vitale, C., and Rosano, G.M. (2013) Androgens and cardiovascular disease: gender-related differences. Menopause Int., 19, 82-86.
82. Oury, F. (2012) A crosstalk between bone and gonads. Ann. N. Y. Acad. Sci., 1260, 1-7.
83. Sutton-Tyrrell, K., Wildman, R.P., Matthews, K.A., Chae, C., Lasley, B.L., Brockwell, S., Pasternak, R.C., Lloyd-Jones, D., Sowers, M.F., Torrens, J.I., and Investigators, S. (2005) Sex hormone-binding globulin and the free androgen index are related to cardiovascular risk factors in multiethnic premenopausal and perimenopausal women enrolled in the Study of Women Across the Nation (SWAN). Circulation, 111, 1242-1249.
84. Hak, A.E., Witteman, J.C., de Jong, F.H., Geerlings, M.I., Hofman, A., and Pols, H.A. (2002) Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. J. Clin. Endocrinol. Metab., 87, 3632-3639.
85. Vassalle, C. and Iervasi, G. (2013) Cathepsin K--a classical bone biomarker in cardiovascular disease: the heart is not alone anymore. Atherosclerosis, 228, 36-37.
86. Turk, V., Turk, B., and Turk, D. (2001) Lysosomal cysteine proteases: facts and opportunities. EMBO J., 20, 4629-4633.
87. Balachandran, K., Sucosky, P., Jo, H., and Yoganathan, A.P. (2009) Elevated cyclic stretch alters matrix remodeling in aortic valve cusps: implications for degenerative aortic valve disease. Am. J. Physiol. Heart Circ. Physiol., 296, 756-764.
88. Platt, M.O., Ankeny, R.F., Shi, G.P., Weiss, D., Vega, J.D., Taylor, W.R., and Jo, H. (2007) Expression of cathepsin K is regulated by shear stress in cultured endothelial cells and is increased in endothelium in human atherosclerosis. Am. J. Physiol. Heart Circ. Physiol., 292, 1479-1486.
89. Chatzizisis, Y.S., Baker, A.B., Sukhova, G.K., Koskinas, K.C., Papafaklis, M.I., Beigel, R., Jonas, M., Coskun, A.U., Stone, B.V., Maynard, C., Shi, G.P., Libby, P., Feldman, C.L., Edelman, E.R., and Stone, P.H. (2011) Augmented expression and activity of extracellular matrix-degrading enzymes in regions of low endothelial shear stress colocalize with coronary atheromata with thin fibrous caps in pigs. Circulation, 123, 621-630.
90. Sukhova, G.K., Shi, G.P., Simon, D.I., Chapman, H.A., and Libby, P. (1998) Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. J. Clin. Invest., 102, 576-583.
91. Lutgens, E., Lutgens, S.P., Faber, B.C., Heeneman, S., Gijbels, M.M., de Winther, M.P., Frederik, P., van der Made, I., Daugherty, A., Sijbers, A.M., Fisher, A., Long, C.J., Saftig, P., Black, D., Daemen, M.J., and Cleutjens, K.B. (2006) Disruption of the cathepsin K gene reduces atherosclerosis progression and induces plaque fibrosis but accelerates macrophage foam cell formation. Circulation, 113, 98-107.
92. Barascuk, N., Skjøt-Arkil, H., Register, T.C., Larsen, L., Byrjalsen, I., Christiansen, C., and Karsdal, M.A. (2010) Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes. BMC Cardiovasc. Disord., 10, 19.
93. Guo, J., Bot, I., de Nooijer, R., Hoffman, S.J., Stroup, G.B., Biessen, E.A., Benson, G.M., Groot, P.H., Van Eck, M., and Van Berkel, T.J. (2009) Leucocyte cathepsin K affects atherosclerotic lesion composition and bone mineral density in low-density lipoprotein receptor deficient mice. Cardiovasc. Res., 81, 278-285.
94. Lindstedt, L., Lee, M., Oorni, K., Bromme, D., and Kovanen, P.T. (2003) Cathepsins F and S block HDL3-induced cholesterol efflux from macrophage foam cells. Biochem. Biophys. Res. Commun., 312, 1019-1024.
95. Cheng, X.W., Kuzuya, M., Sasaki, T., Arakawa, K., Kanda, S., Sumi, D., Koike, T., Maeda, K., Tamaya-Mori, N., Shi, G.P., Saito, N., and Iguchi, A. (2004) Increased expression of elastolytic cysteine proteases, cathepsins S and K, in the neointima of ballooninjured rat carotid arteries. Am. J. Pathol., 164, 243-251.
96. Aikawa, E., Nahrendorf, M., Figueiredo, J.L., Swirski, F.K., Shtatland, T., Kohler, R.H., Jaffer, F.A., Aikawa, M., and Weissleder, R. (2007) Osteogenesis associates with inflammation in earlystage atherosclerosis imaging in vivo. Circulation, 116, 2841-2850.
97. Helske, S., Syvaranta, S., Lindstedt, K.A., Lappalainen, J., Oorni, K., Mayranpaa, M.I., Lommi, J., Turto, H., Werkkala, K., Kupari, M., and Kovane, P.T. (2006) Increased expression of elastolytic cathepsins S, K, and V and their inhibitor cystatin C in stenotic aortic valves. Arterioscler. Thromb. Vasc. Biol., 26, 1791-1798.
98. Yang, M., Sun, J., Zhang, T., Liu, J., Zhang, J., Shi, M.A., Darakhshan, F., Guerre-Millo, M., Clement, K., Gelb, B.D., Dolgnov, G., and Shi, G.P. (2008) Deficiency and inhibition of cathepsin K reduce body weight gain and increase glucose metabolism in mice. Arterioscler. Thromb. Vasc. Biol., 28, 2202-2208.
99. Funicello, M., Novelli, M., Ragni, M., Vottari, T., Cocuzza, C., Soriano-Lopez, J., Chiellini, C., Boschi, F., Marzola, P., Masiello, P., Saftig, P., Santini, F., St-Jacques, R., Desmarais, S., Morin, N., Mancini, J., Percival, M.D., Pinchera, A., and Maffei, M. (2007) Cathepsin K null mice show reduced adiposity during the rapid accumulation of fat stores. PLoS One, 2, e683.
100. Hua, Y., Zhang, Y., Dolence, J., Shi, G.P., Ren, J., and Nair, S. (2013) Cathepsin K knockout mitigates high-fat diet-induced cardiac hypertrophy and contractile dysfunction. Diabetes, 62, 498-509.
101. Shalia, K.K., Mashru, M.R., Shah, V.K., Soneji, S.L., and Payannavar, S. (2012) Levels of cathepsins in acute myocardial infarction. Indian Heart J., 64, 290-294.
102. Cheng, X.W., Kikuchi, R., Ishii, H., Yoshikawa, D., Hu, L., Takahashi, R., Shibata, R., Ikeda, N., Kuzuya, M., Okumura, K., and Murohara, T. (2013) Circulating CatK as a potential novel biomarker of coronary artery disease. Atherosclerosis, 228, 211-216.
103. Lim, V. and Clarke, B.L. (2012) New therapeutic targets for osteoporosis: beyond denosumab. Maturitas, 73, 269-272.
104. Oksala, N., Levula, M., Pelto-Huikko, M., Kytömäki, L., Soini, J.T., Salenius, J., Kähönen, M., Karhunen, P.J., Laaksonen, R., Parkkila, S., and Lehtimäki, T. (2010) Carbonic anhydrases II and XII are up-regulated in osteoclast-like cells in advanced human atherosclerotic plaques-Tampere Vascular Study. Ann. Med., 42, 360-370.
105. Manghat, P., Souleimanova, I., Cheung, J., Wierzbicki, A.S., Harrington, D.J., Shearer, M.J., Chowienczyk, P., Fogelman, I., Nerlander, M., Goldsmith, D., and Hampson, G. (2011) Association of bone turnover markers and arterial stiffness in pre-dialysis chronic kidney disease (CKD). Bone, 45, 1127-1132.
106. Kovesdy, C.P. and Quarles, L.D. (2013) The role of fibroblast growth factor-23 in cardiorenal syndrome. Nephron Clin. Pract., 123, 194-201.
107. Nagano, M., Fukami, K., Yamagishi, S., Sakai, K., Kaida, Y., Matsumoto, T., Hazama, T., Tanaka, M., Ueda, S., and Okuda, S. (2011) Tissue level of advanced glycation end products is an independent determinant of highsensitivity C-reactive protein levels in haemodialysis patients. Nephrology (Carlton), 16, 299-303.
108. Moester, M.J., Papapoulos, S.E., Lowik, C.W., and van Bezooijen, R.L. (2010) Sclerostin: current knowledge and future perspectives. Calcif. Tissue Int., 87, 99-107.
109. Kubota, T., Michigami, T., and Ozono, K. (2009) Wnt signaling in bone metabolism. J. Bone Miner. Metab., 27, 265-271.
110. Szulc, P., Bertholon, C., Borel, O., Marchand, F., and Chapurlat, R. (2013) Lower fracture risk in older men with higher sclerostin concentration: a prospective analysis from the MINOS study. J. Bone Miner. Res., 28, 855-864.
111. Zhu, D., Mackenzie, N.C., Millan, J.L., Farquharson, C., and MacRae, V.E. (2011) The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells. PLoS One, 6, e19595.
112. Brandenburg, V.M., Kramann, R., Koos, R., Krüger, T., Schurgers, L., Mühlenbruch, G., Hübner, S., Gladziwa, U., Drechsler, C., and Ketteler, M. (2013) Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study. BMC Nephrol., 14, 219.
113. Claes, K.J., Viaene, L., Heye, S., Meijers, B., d'Haese, P., and Evenepoel, P. (2013) Sclerostin: another vascular calcification inhibitor? J. Clin. Endocrinol. Metab., 98, 3221-3228.
114. Wahl, P. and Wolf, M. (2012) FGF23 in chronic kidney disease. Adv. Exp. Med. Biol., 728, 107-125 (Springer Link Ed).
115. Scialla, J.J., Xie, H., Rahman, M., Anderson, A.H., Isakova, T., Ojo, A., Zhang, X., Nessel, L., Hamano, T., Grunwald, J.E., Raj, D.S., Yang, W., He, J., Lash, J.P., Go, A.S., Kusek, J.W., Feldman, H., and Wolf, M. (2014) The Chronic Renal Insufficiency Cohort (CRIC) study investigators. Fibroblast growth factor-23 and cardiovascular events in CKD. J. Am. Soc. Nephrol., 25, 349-360.
116. Gutiérrez, O.M., Januzzi, J.L., Isakova, T., Laliberte, K., Smith, K., Collerone, G., Sarwar, A., Hoffmann, U., Coglianese, E., Christenson, R., Wang, T.J., deFilippi, C., and Wolf, M. (2009) Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation, 119, 2545-2552.
117. Mirza, M.A., Larsson, A., Melhus, H., Lind, L., and Larsson, T.E. (2009) Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population. Atherosclerosis, 207, 546-551.
118. Parker, B.D., Schurgers, L.J., Brandenburg, V.M., Christenson, R.H., Vermeer, C., Ketteler, M., Shlipak, M.G., Whooley, M.A., and Ix, J.H. (2010) The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: the Heart and Soul Study. Ann. Intern. Med., 152, 640-648.
119. Mizobuchi, M., Towler, D., and Slatopolsky, E. (2009) Vascular calcification: the killer of patients with chronic kidney disease. J. Am. Soc. Nephrol., 20, 1453-1464.
120. Gutiérrez, O.M., Mannstadt, M., Isakova, T., Rauh-Hain, J.A., Tamez, H., Shah, A., Smith, K., Lee, H., Thadhani, R., Jüppner, H., and Wolf, M. (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N. Engl. J. Med., 359, 584-592.
121. Kanbay, M., Nicoleta, M., Selcoki, Y., Ikizek, M., Aydin, M., Eryonucu, B., Duranay, M., Akcay, A., Armutcu, F., and Covic, A. (2010) Fibroblast growth factor 23 and fetuin A are independent predictors for the coronary artery disease extent in mild chronic kidney disease. Clin. J. Am. Soc. Nephrol., 5, 1780-1786.
122. Kanbay, M., Wolf, M., Selcoki, Y., Solak, Y., Ikizek, M., Uysal, S., Segall, L., Armutcu, F., Eryonucu, B., Duranay, M., Goldsmith, D., and Covic, A. (2012) Association of serum calcitonin with coronary artery disease in individuals with and without chronic kidney disease. Int. Urol. Nephrol., 44, 1169-1175.
123. Faul, C., Amaral, A.P., Oskouei, B., Hu, M.C., Sloan, A., Isakova, T., Gutiérrez, O.M., Aguillon-Prada, R., Lincoln, J., Hare, J.M., Mundel, P., Morales, A., Scialla, J., Fischer, M., Soliman, E.Z., Chen, J., Go, A.S., Rosas, S.E., Nessel, L., Townsend, R.R., Feldman, H.I., St John Sutton, M., Ojo, A., Gadegbeku, C., Di Marco, G.S., Reuter, S., Kentrup, D., Tiemann, K., Brand, M., Hill, J.A., Moe, O.W., Kuro-O, M., Kusek, J.W., Keane, M.G., and Wolf, M. (2011) FGF23 induces left ventricular hypertrophy. J. Clin. Invest., 121, 4393-4408.
124. Mirza, M.A., Alsiö, J., Hammarstedt, A., Erben, R.G., Michaëlsson, K., Tivesten, A., Marsell, R., Orwoll, E., Karlsson, M.K., Ljunggren, O., Mellström, D., Lind, L., Ohlsson, C., and Larsson, T.E. (2011) Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals. Arterioscler. Thromb. Vasc. Biol., 31, 219-227.
125. Sodek, J., Ganss, B., and McKee, M.D. (2000) Osteopontin. Crit. Rev. Oral Biol. Med., 11, 279-303.
126. Momiyama, Y., Ohmori, R., Fayad, Z.A., Kihara, T., Tanaka, N., Kato, R., Taniguchi, H., Nagata, M., Nakamura, H., and Ohsuzu, F. (2010) Associations between plasma osteopontin levels and the severities of coronary and aortic atherosclerosis. Atherosclerosis, 210, 668-670.
127. Ohmori, R., Momiyama, Y., Taniguchi, H., Takahashi, R., Kusuhara, M., Nakamura, H., and Ohsuzu, F. (2003) Plasma osteopontin levels are associated with the presence and extent of coronary artery disease. Atherosclerosis, 170, 333-337.
128. Tousoulis, D., Siasos, G., Maniatis, K., Oikonomou, E., Kioufis, S., Zaromitidou, M., Paraskevopoulos, T., Michalea, S., Kollia, C., Miliou, A., Kokkou, E., Papavassiliou, A.G., and Stefanadis, C. (2013) Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease. Int. J. Cardiol., 167, 1924-1928.
129. Abdel-Azeez, H.A. and Al-Zaky, M. (2010) Plasma osteopontin as a predictor of coronary artery disease: association with echocardiographic characteristics of atherosclerosis. J. Clin. Lab. Anal., 24, 201-206.
130. Georgiadou, P., Iliodromitis, E.K., Kolokathis, F., Varounis, C., Gizas, V., Mavroidis, M., Capetanaki, Y., Boudoulas, H., and Kremastinos, D.T. (2010) Osteopontin as a novel prognostic marker in stable ischaemic heart disease: a 3-year follow-up study. Eur. J. Clin. Invest., 40, 288-293.
131. Rosenberg, M., Zugck, C., Nelles, M., Juenger, C., Frank, D., Remppis, A., Giannitsis, E., Katus, H.A., and Frey, N. (2008) Osteopontin, a new prognostic biomarker in patients with chronic heart failure. Circ. Heart Fail., 1, 43-49.
132. Singh, K., Sirokman, G., Communal, C., Robinson, K.G., Conrad, C.H., Brooks, W.W., Bing, O.H., and Colucci, W.S. (1999) Myocaridal osteopontin expression coincides with the development of heart failure. Hypertension, 33, 663-670.
133. Murry, C.E., Giachelli, C.M., Schwartz, S.M., and Vracko, R. (1994) Macrophages express osteopontin during repair of myocardial necrosis. Am. J. Pathol., 145, 1450-1462.
134. Ellison, J.A., Velier, J.J., Spera, P., Jonak, Z.L., Wang, X., Barone, F.C., and Feuerstein, G.Z. (1998) Osteopontin and its integrin receptor alpha(v) beta3 are upregulated during formation of the glial scar after focal stroke. Stroke, 29, 1698-1706.
135. O'Brien, E.R., Garvin, M.R., Stewart, D.K., Hinohara, T., Simpson, J.B., Schwartz, S.M., and Giachelli, C.M. (1994) Osteopontin is synthesized by macrophage, smooth muscle, and endothelial cells in primary and restenotic human coronary atherosclerotic plaques. Arterioscler. Thromb., 14, 1648-1656.
136. Kato, R., Momiyama, Y., Ohmori, R., Tanaka, N., Taniguchi, H., Arakawa, K., Kusuhara, M., Nakamura, H., and Ohsuzu, F. (2006) High plasma levels of osteopontin in patients with restenosis after percutaneous coronary intervention. Arterioscler. Thromb. Vasc. Biol., 26, e1-e2.
137. Singh, M., Foster, C.R., Dalal, S., and Singh, K. (2010) Role of osteopontin in heart failure associated with aging. Heart Fail. Rev., 15, 487-494.
138. Okamoto, H. and Imanaka-Yoshida, K. (2012) Matricellular proteins: new molecular targets to prevent heart failure. Cardiovasc. Ther., 30, 198-209.
139. Scatena, M., Liaw, L., and Giachelli, C.M. (2007) Osteopontin: a multifunctional molecule regulating chronic inflammation and vascular disease. Arterioscler. Thromb. Vasc. Biol., 27, 2302-2309.
140. Wada, T., McKee, M.D., Steitz, S., and Giachelli, C.M. (1999) Calcification of vascular smooth muscle cell cultures: inhibition by osteopontin. Circ. Res., 84, 166-178.
141. Yu, J.P., Skolnick, A., Ferrari, G., Heretis, K., Mignatti, P., Pintucci, G., Rosenzweig, B., Diaz-Cartelle, J., Kronzon, I., Perk, G., Pass, H.I., Galloway, A.C., Grossi, E.A., and Grau, J.B. (2009) Correlation between Plasma Osteopontin Levels and aortic valve calcification: potential insights into the pathogenesis of aortic valve calcification and stenosis. J. Thorac. Cardiovasc. Surg., 138, 196-199.
142. Jono, S., Peinado, C., and Giachelli, C.M. (2000) Phosphorylation of osteopontin is required for inhibition of vascular smooth muscle cell calcification. J. Biol. Chem., 275, 20197-20203.
143. Kazanecki, C.C., Uzwiak, D.J., and Denhardt, D.T. (2007) Control of osteopontin signaling and function by post-translational phosphorylation and protein folding. J. Cell. Biochem., 102, 912-924.
144. Sainger, R., Grau, J.B., Poggio, P., Branchetti, E., Bavaria, J.E., Gorman, J.H. III, Gorman, R.C., and Ferrari, G. (2012) Dephosphorylation of circulating human osteopontin correlates with severe valvular calcification in patients with calcific aortic valve disease. Biomarkers, 17, 111-118.
145. Neve, A., Corrado, A., and Cantatore, F.P. (2013) Osteocalcin: skeletal and extra-skeletal effects. J. Cell. Physiol., 228, 1149-1153.
146. Lee, N.K., Sowa, H., Hinoi, E., Ferron, M., Ahn, J.D., Confavreux, C., Dacquin, R., Mee, P.J., McKee, M.D., Jung, D.Y., Zhang, Z., Kim, J.K., Mauvais-Jarvis, F., Ducy, P., and Karsenty, G. (2007) Endocrine regulation of energy metabolism by skeleton. Cell, 130, 456-469.
147. Fernández-Real, J.M., Izquierdo, M., Ortega, F., Gorostiaga, E., Gómez-Ambrosi, J., Moreno-Navarrete, J.M., Frühbeck, G., Martínez, C., Idoate, F., Salvador, J., Forga, L., Ricart, W., and Ibañez, J. (2009) The relationship between serum osteoclacin concentration to insulin secretion, sensitivity, and disposal with hipocaloric diet and resistance training. J. Clin. Endocrinol. Metab., 94, 237-245.
148. Pittas, A.G., Harris, S.S., Eliades, M., Stark, P., and Dawson-Hughes, B. (2009) Association between serum osteocalcin and markers of metabolic phenotype. J. Clin. Endocrinol. Metab., 94, 827-832.
149. Kanazawa, I., Yamaguchi, T., Yamamoto, M., Yamauchi, M., Kurioka, S., Yano, S., and Sugimoto, T. (2009) Serum osteocalcin level is associated with glucose metabolism and atheroesclerosis parameters in type 2 diabetes mellitus. J. Clin. Endocrinol. Metab., 94, 45-49.
150. Zhang, Y., Qi, L., Gu, W., Yan, Q., Dai, M., Shi, J., Zhai, Y., Chen, Y., Liu, J., Wang,W., Ning, G., and Hong, J. (2010) Relation of serum osteocalcin level to risk of coronary heart disease in Chinese adults. Am. J. Cardiol., 106, 1461-1465.
151. Sheng, L., Cao, W., Cha, B., Chen, Z., Wang, F., and Liu, J. (2013) Serum osteocalcin level and its association with carotid atherosclerosis in patients with type 2 diabetes. Cardiovasc. Diabetol., 12, 22.
152. Goliasch, G., Blessberger, H., Azar, D., Heinze, G.,Wojta, J., Bieglmayer, C., Wagner, O., Schillinger, M., Huber, K., Maurer, G., Haas, M., and Wiesbauer, F. (2011) Markers of bone metabolism in premature myocardial infarction (=40 years of age). Bone, 48, 622-626.
153. Yang, R., Ma, X., Dou, J., Wang, F., Luo, Y., Li, D., Zhu, J., Bao, Y., and Jia, W. (2013) Relationship between serum osteocalcin levels and carotid intima-media thickness in Chinese postmenopausal women. Menopause, 20, 1194-1199.
154. Montalcini, T., Emanuele, V., Ceravolo, R., Gorgone, G., Sesti, G., Perticone, F., and Pujia, A. (2004) Relation of low bone mineral density and carotid atheroesclerosis in postmenopausal women. Am. J. Cardiol., 94, 266-269.
155. Fernández-Real, J.M. and Ricart, W. (2011) Osteocalcin: a new link between bone and energy metabolism. Some evolutionary clues. Curr. Opin. Clin. Nutr. Metab. Care, 14, 360-366.
156. Hwang, Y.C., Jeong, I.K., Ahn, K.J., and Chung, H.Y. (2009) The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle aged male subjects. Diabetes Metab. Res. Rev., 25, 768-772.
157. Mizokami, A., Yasutake, Y., Gao, J., Matsuda, M., Takahashi, I., Takeuchi, H., and Hirata, M. (2013) Osteocalcin induces release of glucagon-like peptide-1 and thereby stimulates insulin secretion in mice. PLoS One, 8, e57375.
158. Villafán-Bernal, J.R., Llamas-Covarrubias, M.A., Muñoz-Valle, J.F., Rivera-León, E.A., González-Hita, M.E., Bastidas-Ramírez, B.E., Gurrola-Díaz, C.M., Armendáriz-Borunda, J.S., and Sánchez-Enríquez, S. (2014) A cut-point value of uncarboxylated to carboxylated index is associated with glycemic status markers in type 2 diabetes. J. Investig. Med., 62, 33-36.
159. Gössl, M., Mödder, U.I., Atkinson, E.J., Lerman, A., and Khosla, S. (2008) Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis. J. Am. Coll. Cardiol., 52, 1314-1325.
160. Flammer, A.J., Gössl, M., Widmer, R.J., Reriani, M., Lennon, R., Loeffler, D., Shonyo, S., Simari, R.D., Lerman, L.O., Khosla, S., and Lerman, A. (2012) Osteocalcin positive CD133+/CD34- /KDR+ progenitor cells as an independent marker for unstable atherosclerosis. Eur. Heart J., 33, 2963-2969.
161. Hofbauer, L.C., Khosla, S., Dunstan, C.R., Lacey, D., Boyle,W.J., and Riggs, B.L. (2000) The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J. Bone Miner. Res., 15, 2-12.
162. Min, H., Morony, S., Sarosi, I., Dunstan, C.R., Capparelli, C., Scully, S., Van, G., Kaufman, S., Kostenuik, P.J., Lacey, D.L., Boyle, W.J., and Simonet, W.S. (2000) Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis. J. Exp. Med., 192, 463-474.
163. Van Campenhout, A. and Golledge, J. (2009) Osteoprotegerin, vascular calcification and atherosclerosis. Atherosclerosis, 204, 321-329.
164. Bucay, N., Sarosi, I., Dunstan, C.R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H.L., Xu, W., Lacey, D.L., Boyle, W.J., and Simonet, W.S. (1998) Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev., 12, 1260-1268.
165. Yun, T.J., Tallquist, M.D., Aicher, A., Rafferty, K.L., Marshall, A.J., Moon, J.J., Ewings, M.E., Mohaupt, M., Herring, S.W., and Clark, E.A. (2001) Osteoprotegerin a crucial regulator of bone metabolism, also regulates B cell development and function. J. Immunol., 166, 1482-1491.
166. Price, P.A., June, H.H., Buckley, J.R., and Williamson, M.K. (2001) Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin D. Arterioscler. Thromb. Vasc. Biol., 21, 1610-1616.
167. Golledge, J., McCann, M., Mangan, S., Lam, A., and Karan, M. (2004) Osteoprotegerin and osteopontin are expressed at high concentrations within symptomatic carotid atherosclerosis. Stroke, 35, 1636-1641.
168. Sandberg, W.J., Yndestad, A., Øie, E., Smith, C., Ueland, T., Ovchinnikova, O., Robertson, A.K., Müller, F., Semb, A.G., Scholz, H., Andreassen, A.K., Gullestad, L., Damås, J.K., Frøland, S.S., Hansson, G.K., Halvorsen, B., and Aukrust, P. (2006) Enhanced T-cell expression of RANK ligand in acute coronary syndrome: possible role in plaque destabilization. Arterioscler. Thromb. Vasc. Biol., 26, 857-863.
169. Blázquez-Medela, A.M., García-Ortiz, L., Gómez-Marcos, M.A., Recio-Rodriguez, J.I., Sánchez-Rodríguez, A., López-Novoa, J.M., and Martínez-Salgado, C. (2012) Osteoprotegerin is associated with cardiovascular risk in hypertension and/or diabetes. Eur. J. Clin. Invest., 42, 548-556.
170. Montagnana, M., Lippi, G., Danese, E., and Guidi, G.C. (2013) The role of osteoprotegerin in cardiovascular disease. Ann. Med., 45, 254-264.
171. Hosbond, S.E., Poulsen, T.S., Diederichsen, A.C., Nybo, M., Rasmussen, L.M., and Mickley, H. (2012) Osteoprotegerin as a marker of atherosclerosis: a systematic update. Scand. Cardiovasc. J., 46, 203-211.
172. Mogelvang, R., Pedersen, S.H., Flyvbjerg, A., Bjerre, M., Iversen, A.Z., Galatius, S., Frystyk, J., and Jensen, J.S. (2012) Comparison of osteoprotegerin to traditional atherosclerotic risk factors and high-sensitivity C-reactive protein for diagnosis of atherosclerosis. Am. J. Cardiol., 109, 515-520.
173. Fontes, J.D., Yamamoto, J.F., Larson, M.G., Wang, N., Dallmeier, D., Rienstra, M., Schnabel, R.B., Vasan, R.S., Keaney, J.F. Jr., and Benjamin, E.J. (2013) Clinical correlates of change in inflammatory biomarkers: the Framingham Heart Study. Atherosclerosis, 228, 217-223.
174. Shargorodsky, M., Boaz, M., Luckish, A., Matas, Z., Gavish, D., and Mashavi, M. (2009) Osteoprotegerin as an independent marker of subclinical atherosclerosis in osteoporotic postmenopausal women. Atherosclerosis, 204, 608-611.
175. Løgstrup, B.B., Høfsten, D.E., Christophersen, T.B., Møller, J.E., Bjerre, M., Flyvbjerg, A., Bøtker, H.E., and Egstrup, K. (2013) Microvascular dysfunction is associated with plasma osteoprotegerin levels in patients with acute myocardial infarction. Coron. Artery Dis., 24, 487-492.
176. Jono, S., Ikari, Y., Shioi, A., Mori, K., Miki, T., Hara, K., and Nishizawa, Y. (2002) Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation, 106, 1192-1194.
177. Schoppet, M., Sattler, A.M., Schaefer, J.R., Herzum, M., Maisch, B., and Hofbauer, L.C. (2003) Increased osteoprotegerin serum levels in men with coronary artery disease. J. Clin. Endocrinol. Metab., 88, 1024-1028.
178. Ziegler, S., Kudlacek, S., Luger, A., and Minar, E. (2005) Osteoprotegerin plasma concentrations correlate with severity of peripheral artery disease. Atherosclerosis, 182, 175-180.
179. Browner, W.S. and Lui, L.Y. (2001) Cummings SR Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J. Clin. Endocrinol. Metab., 86, 631-637.
180. Kiechl, S., Schett, G., Wenning, G., Redlich, K., Oberhollenzer, M., Mayr, A., Santer, P., Smolen, J., Poewe, W., and Willeit, J. (2004) Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation, 109, 2175-2180.
181. Lieb, W., Gona, P., Larson, M.G., Massaro, J.M., Lipinska, I., Keaney, J.F. Jr., Rong, J., Corey, D., Hoffmann, U., Fox, C.S., Vasan, R.S., Benjamin, E.J., O'Donnell, C.J., and Kathiresan, S. (2010) Biomarkers of the osteoprotegerin pathway: clinical correlates, subclinical disease, incident cardiovascular disease, and mortality. Arterioscler. Thromb. Vasc. Biol., 30, 1849-1854.
182. Yang, Q., Lu, S., Chen, Y., Song, X., Jin, Z., Yuan, F., Li, H., Zhou, Y., Chen, F., and Huo, Y. (2011) Plasma osteoprotegerin levelsand long-term prognosis in patients with intermediate coronary artery lesions. Clin. Cardiol., 34, 447-453.
183. Pedersen, E.R., Ueland, T., Seifert, R., Aukrust, P., Schartum-Hansen, H., Ebbing, M., Bleie, Ø., Igland, J., Svingen, G., Nordrehaug, J.E., and Nygård, O. (2010) Serum osteoprotegerin levels and long-term prognosis in patients with stable angina pectoris. Atherosclerosis, 212, 644-649.
184. Mogelvang, R., Haahr-Pedersen, S., Bjerre, M., Frystyk, J., Iversen, A., Galatius, S., Flyvbjerg, A., and Jensen, J.S. (2013) Osteoprotegerin improves risk detection by traditional cardiovascular risk factors and hsCRP. Heart, 99, 106-110.
185. Çanga, A., Durakoğlugil, M.E., Erdoğan, T., Kirbas, A., Yilmaz, A., çiçek, Y., Ergül, E., Çetin, M., and Kocaman, S.A. (2012) Elevated serum osteoprotegerin levels predict in-hospital major adverse cardiac events in patients with ST elevation myocardial infarction. J. Cardiol., 60, 355-360.
186. Song, T.J., Kim, J., Yang, S.H., Park, J.H., Lee, H.S., Nam, C.M., Lee, O.H., Kim, Y.D., Nam, H.S., and Heo, J.H. (2012) Association of plasma osteoprotegerin levels with stroke severity and functional outcome in acute ischaemic stroke patients. Biomarkers, 17, 738-744.
187. Omland, T., Ueland, T., Jansson, A.M., Persson, A., Karlsson, T., Smith, C., Herlitz, J., Aukrust, P., Hartford, M., and Caidahl, K. (2008) Circulating osteoprotegerin levels and long-term prognosis in patients with acute coronary syndromes. J. Am. Coll. Cardiol., 51, 627-633.
188. Secchiero, P., Corallini, F., Beltrami, A.P., Ceconi, C., Bonasia, V., Di Chiara, A., Ferrari, R., and Zauli, G. (2010) An imbalanced OPG/TRAIL ratio is associated to severe acute myocardial infarction. Atherosclerosis, 210, 274-277.
189. Ueland, T., Jemtland, R., Godang, K., Kjekshus, J., Hognestad, A., Omland, T., Squire, I.B., Gullestad, L., Bollerslev, J., Dickstein, K., and Aukrust, P. (2004) Prognostic value of osteoprotegerin in heart failure after acute myocardial infarction. J. Am. Coll. Cardiol., 44, 1970-1976.
190. Roysland, R., Masson, S., Omland, T., Milani, V., Bjerre, M., Flyvbjerg, A., Di Tano, G., Misuraca, G., Maggioni, A.P., Tognoni, G., Tavazzi, L., and Latini, R. (2010) Prognostic value of osteoprotegerin in chronic heart failure: the GISSI-HF trial. Am. Heart J., 160, 286-293.
191. Augoulea, A., Vrachnis, N., Lambrinoudaki, I., Dafopoulos, K., Iliodromiti, Z., Daniilidis, A., Varras, M., Alexandrou, A., Deligeoroglou, E., and Creatsas, G. (2013) Osteoprotegerin as a marker of atherosclerosis in diabetic patients. Int. J. Endocrinol. doi: 10.1155/2013/182060.
192. Xiang, G.D., Sun, H.L., and Zhao, L.S. (2007) Changes of osteoprotegerin before and after insulin therapy in type diabetic patients. Diabetes Res. Clin. Pract., 76, 199-206.
193. Rasmussen, L.M., Tarnow, L., Hansen, T.K., Parving, H.H., and Flyvbjerg, A. (2006) Plasma osteoprotegerin levels are associated with glycaemic status, systolic blood pressure, kidney function and cardiovascular mordibity in type diabetic patients. Eur. J. Endocrinol., 154, 75-81.
194. Chen, W.J., Rijzewijk, L.J., van der Meer, R.W., Heymans, M.W., van Duinkerken, E., Lubberink, M., Lammertsma, A.A., Lamb, H.J., de Roos, A., Romijn, J.A., Smit, J.W., Bax, J.J., Bjerre, M., Frystyk, J., Flyvbjerg, A., and Diamant, M. (2011) Association of plasma osteoprotegerin and adiponectin with arterial function, cardiac function and metabolism in asymptomatic type diabetic men. Cardiovasc. Diabetol., 10, 67.
195. Akinci, B., Demir, T., Celtik, A., Baris, M., Yener, S., Ozcan, M.A., Yuksel, F., Secil, M., and Yesil, S. (2008) Serum osteoprotegerin is associated with carotid intima media thickness in women with previous gestational diabetes. Diabetes Res. Clin. Pract., 82, 172-178.
196. Galluzzi, F., Stagi, S., Salti, R., Toni, S., Piscitelli, E., Simonini, G., and Falcini, F. (2005) Chiarelli F Osteoprotegerin serum levels in children with type 1 diabetes: a potential modulating role in bone status. Eur. J. Endocrinol., 153, 879-885.
197. Vaccarezza, M., Bortul, R., Fadda, R., and Zweyer, M. (2007) Increased OPG expression and impaired OPG/TRAIL ratio in the aorta of diabetic rats. Med. Chem., 3, 387-391.
198. Bjerre, M. (2013) Osteoprotegerin (OPG) as a biomarker for diabetic cardiovascular complications. Springerplus, 2, 658.
199. Knudsen, S.T., Foss, C.H., Poulsen, P.L., Andersen, N.H., Mogensen, C.E., and Rasmussen, L.M. (2003) Increased plasma concentrations of osteoprotegerin in type 2 diabetic patients with microvascular complications. Eur. J. Endocrinol., 149, 39-42.
200. Aoki, A., Murata, M., Asano, T., Ikoma, A., Sasaki, M., Saito, T., Otani, T., Jinbo, S., Ikeda, N., Kawakami, M., and Ishikawa, S.E. (2013) Association of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes. Cardiovasc. Diabetol., 12, 11.
201. Dallmeier, D., Larson, M.G., Wang, N., Fontes, J.D., Benjamin, E.J., and Fox, C.S. (2012) Addition of inflammatory biomarkers did not improve diabetes prediction in the community: the framingham heart study. J. Am. Heart Assoc., 1, e000869.
202. Abedin, M., Omland, T., Ueland, T., Khera, A., Aukrust, P., Murphy, S.A., Jain, T., Gruntmanis, U., McGuire, D.K., and de Lemos, J.A. (2007) Relation of osteoprotegerin to coronary calcium and aortic plaque (from the Dallas Heart Study). Am. J. Cardiol., 99, 513-518.
203. Zauli, G., Corallini, F., Bossi, F., Fischetti, F., Durigutto, P., Celeghini, C., Tedesco, F., and Secchiero, P. (2007) Osteoprotegerin increases leukocyte adhesion to endothelial cells both in vitro and in vivo. Blood, 110, 536-543.
204. Mangan, S.H., Campenhout, A.V., Rush, C., and Golledege, J. (2007) Osteoprotegerin upregulates endothelial cell adhesion molecule response to tumour necrosis factor-a associated with induction of angiopoietin-2. Cardiovasc. Res., 76, 494-505.
205. Vassalle, C. and Pérez-López, F.R. (2013) The importance of some analytical aspects and confounding factors in relation to clinical interpretation of results, in Vitamin D: Daily Requirements, Dietary Sources and Symptoms of Deficiency, Chapter 4, Nova Publisher. ISBN: 978-1-62808-816-8.
206. Gunta, S.S., Thadhani, R.I., and Mak, R.H. (2013) The effect of vitamin D status on risk factors for cardiovascular disease. Nat. Rev. Nephrol., 9, 337-347.
207. Song, Y., Wang, L., Pittas, A.G., Del Gobbo, L.C., Zhang, C., Manson, J.E., and Hu, F.B. (2013) Blood 25- hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care, 36, 1422-1428.
208. Wang, L., Song, Y., Manson, J.E., Pilz, S., März, W., Michaëlsson, K., Lundqvist, A., Jassal, S.K., Barrett-Connor, E., Zhang, C., Eaton, C.B., May, H.T., Anderson, J.L., and Sesso, H.D. (2012) Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ. Cardiovasc. Qual. Outcomes, 5, 819-829.
209. Giovannucci, E., Liu, Y., Hollis, B.W., and Rimm, E.B. (2008) 25- hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch. Intern. Med., 168, 1174-1180.
210. Dror, Y., Giveon, S.M., Hoshen, M., Feldhamer, I., Balicer, R.D., and Feldman, B.S. (2013) Vitamin D levels for preventing acute coronary syndrome and mortality: evidence of a nonlinear association. J. Clin. Endocrinol. Metab., 98, 2160-2167.
211. Brøndum-Jacobsen, P., Nordestgaard, B.G., Schnohr, P., and Benn, M. (2013) 25-hydroxyvitamin D and symptomatic ischemic stroke: an original study and meta-analysis. Ann. Neurol., 73, 38-47.
212. Kent, S.T., McClure, L.A., Judd, S.E., Howard, V.J., Crosson, W.L., Al-Hamdan, M.Z., Wadley, V.G., Peace, F., and Kabagambe, E.K. (2013) Short and long-term sunlight radiation and stroke incidence. Ann. Neurol., 73, 32-37.
213. Meredith, A.J. and McManus, B.M. (2013) Vitamin D in heart failure. J. Card. Fail., 19, 692-711.
214. Melamed, M.L., Muntner, P., Michos, E.D., Uribarri, J., Weber, C., Sharma, J., and Raggi, P. (2008) Serum 25- hydroxyvitamin D levels and the prevalence of peripheral arterial disease: results from NHANES 2001 to Arterioscler. Thromb. Vasc. Biol., 28, 1179-1185.
215. Ng, L.L., Sandhu, J.K., Squire, I.B., Davies, J.E., and Jones, D.J. (2013) Vitamin D and prognosis in acute myocardial infarction. Int. J. Cardiol., 168, 2341-2346.
216. Correia, L.C., Sodré, F., Garcia, G., Sabino, M., Brito, M., Kalil, F., Barreto, B., Lima, J.C., and Noya-Rabelo, M.M. (2013) Relation of severe deficiency of vitamin D to cardiovascular mortality during acute coronary syndromes. Am. J. Cardiol., 111, 324-327.
217. Brøndum-Jacobsen, P., Benn, M., Jensen, G.B., and Nordestgaard, B.G. (2012) 25-hydroxyvitamin d levels and risk of ischemic heart disease, myocardial infarction, and early death: population-based study and meta-analyses of 18 and 17 studies. Arterioscler. Thromb. Vasc. Biol., 32, 2794-2802.
218. Tomson, J., Emberson, J., Hill, M., Gordon, A., Armitage, J., Shipley, M., Collins, R., and Clarke, R. (2013) Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12,000 deaths. Eur. Heart J., 34, 1365-1374.
219. Hsia, J., Heiss, G., Ren, H., Allison, M., Dolan, N.C., Greenland, P., Heckbert, S.R., Johnson, K.C., Manson, J.E., Sidney, S., Trevisan, M., and Women's Health Initiative Investigators (2007) Calcium/vitamin D supplementation and cardiovascular events. Circulation, 115, 846-854.
220. Wang, L., Manson, J.E., Song, Y., and Sesso, H.D. (2010) Systematic review: vitamin D and calcium supplementation in prevention of cardiovascular events. Ann. Intern. Med., 152, 315-323.
221. Beveridge, L.A. and Witham, M.D. (2013) Vitamin D and the cardiovascular system. Osteoporos. Int., 24, 2167-2180.
222. Christakos, S. and DeLuca, H.F. (2011) Minireview: vitamin D: is there a role in extraskeletal health? Endocrinology, 152, 2930-2936.
223. Bianchi, S., Maffei, S., Prontera, C., Battaglia, D., and Vassalle, C. (2012) Preanalytical, analytical (DiaSorin LIAISON) and clinical variables potentially affecting the 25-OH vitamin D estimation. Clin. Biochem., 45, 1652-1657.
224. Tomaschitz, A., Pilz, S., Ritz, E., Grammer, T., Drechsler, C., Boehm, B.O., and März, W. (2010) Independent association between 1,25- dihydroxyvitamin D, 25-hydroxyvitamin D and the renin-angiotensin system: the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Clin. Chim. Acta, 411, 1354-1360.
225. Simpson, R.U. and Hershey, S.H. (2007) Nibbelink KA characterization of heart size and blood pressure in the vitamin D receptor knockout mouse. J. Steroid Biochem. Mol. Biol., 103, 521-552.
226. Guillot, X., Semerano, L., Saidenberg-Kermanac'h, N., Falgarone, G., and Boissier, M.C. (2010) Vitamin D and inflammation. Joint Bone Spine, 77, 552-557.
227. Uberti, F., Lattuada, D., Morsanuto, V., Nava, U., Bolis, G., Vacca, G., Squarzanti, D.F., Cisari, C., and Molinari, C. (2014) Vitamin D protects human endothelial cells from oxidative stress through the autophagic and survival pathways. J. Clin. Endocrinol. Metab., 99, 1367-1374.
228. Sundström, J. and Vasan, R.S. (2006) Circulating biomarkers of extracellular matrix remodeling and risk of atherosclerotic events. Curr. Opin. Lipidol., 17, 45-53.
229. Pater, A., Sypniewska, G., and Pilecki, O. (2010) Biochemical markers of bone cell activity in children with type 1 diabetes mellitus. J. Pediatr. Endocrinol. Metab., 23, 81-86.
230. Achemlal, L., Tellal, S., Rkiouak, F., Nouijai, A., Bezza, A., Derouiche el, M., Ghafir, D., and El Maghraoui, A. (2005) Bone metabolism in male patients with type 2 diabetes. Clin. Rheumatol., 24, 493-496.
231. Ricci, T.A., Chowdhury, H.A., Heymsfield, S.B., Stahl, T., Pierson, R.N. Jr., and Shapses, S.A. (1998) Calcium supplementation suppresses bone turnover during weight reduction in postmenopausal women. J. Bone Miner. Res., 13, 1045-1050.
232. Ricci, T.A., Heymsfield, S.B., Pierson, R.N. Jr., Stahl, T., Chowdhury, H.A., and Shapses, S.A. (2001) Moderate energy restriction increases bone resorption in obese postmenopausal women. Am. J. Clin. Nutr., 73, 347-352.
233. Shapses, S.A., Von Thun, N.L., Heymsfield, S.B., Ricci, T.A., Ospina, M., Pierson, R.N., and Stahl, T. (2001) Bone turnover and density in obese premenopausal women during moderate weight loss and calcium supplementation. J. Bone Miner. Res., 16, 1329-1336.
234. Giusti, V., Gasteyger, C., Suter, M., Heraief, E., Gaillard, R.C., and Burckhardt, P. (2005) Gastric banding induces negative bone remodelling in the absence of secondary hyperparathyroidism: potential role of serum C telopeptides for follow-up. Int. J. Obes. (Lond), 29, 1429-1435.
235. Noakes, M., Keogh, J.B., Foster, P.R., and Clifton, P.M. (2005) Effect of an energy-restricted, high-protein, low-fat diet relative to a conventional highcarbohydrate, low-fat diet on weight loss, body composition, nutritional status, and markers of cardiovascular health in obese women. Am. J. Clin. Nutr., 81, 1298-1306.
236. Hinton, P.S., LeCheminant, J.D., Smith, B.K., Rector, R.S., and Donnelly, J.E. (2009) Weight loss-induced alterations in serum markers of bone turnover persist during weight maintenance in obese men and women. J. Am. Coll. Nutr., 28, 565-573.
237. Eriksen, H.A., Satta, J., Risteli, J., Veijola, M., Väre, P., and Soini, Y. (2006) Type I and type III collagen synthesis and composition in the valve matrix in aortic valve stenosis. Atherosclerosis, 189, 91-98.
238. Lerchbaum, E., Schwetz, V., Pilz, S., Grammer, T.B., Look, M., Boehm, B.O., Obermayer-Pietsch, B., and März, W. (2013) Association of bone turnover markers with mortality in men referred to coronary angiography. Osteoporos. Int., 24, 1321-1332.
239. Byon, C.H., Javed, A., Dai, Q., Kappes, J.C., Clemens, T.L., Darley-Usmar, V.M., McDonald, J.M., and Chen, Y. (2008) Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling. J. Biol. Chem., 283, 15319-15327.
240. Naik, V., Leaf, E.M., Hu, J.H., Yang, H.Y., Nguyen, N.B., Giachelli, C.M., and Speer, M.Y. (2012) Sources of cells that contribute to atherosclerotic intimal calcification: an in vivo genetic fate mapping study. Cardiovasc. Res., 94, 545-554.
241. Bobryshev, Y.V., Killingsworth, M.C., and Lord, R.S. (2008) Spatial distribution of osteoblast-specific transcription factor Cbfa1 and bone formation in atherosclerotic arteries. Cell Tissue Res., 333, 225-235.
242. Aikawa, E., Nahrendorf, M., Sosnovik, D., Lok, V.M., Jaffer, F.A., Aikawa, M., and Weissleder, R. (2007) Multimodality molecular imaging identifies proteolytic and osteogenic activities in early aortic valve disease. Circulation, 115, 377-386.
243. Huang, J., Huang, H., Wu, M., Li, J., Xie, H., Zhou, H., Liao, E., and Peng, Y. (2013) Connective tissue growth factor induces osteogenic differentiation of vascular smooth muscle cells through ERK signaling. Int. J. Mol. Med., 32, 423-429.
244. Sun, Y., Byon, C.H., Yuan, K., Chen, J., Mao, X., Heath, J.M., Javed, A., Zhang, K., Anderson, P.G., and Chen, Y. (2012) Smooth muscle cell-specific runx2 deficiency inhibits vascular calcification. Circ. Res., 111, 543-552.
245. Luo, G., Ducy, P., McKee, M.D., Pinero, G.J., Loyer, E., Behringer, R.R., and Karsenty, G. (1997) Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature, 386, 78-81.
246. Yao, Y., Bennett, B.J., Wang, X., Rosenfeld, M.E., Giachelli, C., Lusis, A.J., and Boström, K.I. (2010) Inhibition of bone morphogenetic proteins protects against atherosclerosis and vascular calcification. Circ. Res., 107, 485-494.
247. Jia, G., Stormont, R.M., Gangahar, D.M., and Agrawal, D.K. (2012) Role of matrix Gla protein in angiotensin II-induced exacerbation of vascular calcification. Am. J. Physiol. Heart Circ. Physiol., 303, H523-H532.
248. Jono, S., Shioi, A., Ikari, Y., and Nishizawa, Y. (2006) Vascular calcification in chronic kidney disease. J. Bone Miner. Metab., 24, 176-181.
249. Shanahan, C.M., Cary, N.R., Salisbury, J.R., Proudfoot, D.,Weissberg, P.L., and Edmonds, M.E. (1999) Medial localization of mineralization-regulating proteins in association with Monckeberg's sclerosis: evidence for smooth muscle cell-mediated vascular calcification. Circulation, 100, 2168-2176.
250. Braam, L.A., Dissel, P., Gijsbers, B.L., Spronk, H.M., Hamulyak, K., Soute, B.A., Debie, W., and Vermeer, C. (2000) Assay for human matrix gla protein in serum: potential applications in the cardiovascular field. Arterioscler. Thromb. Vasc. Biol., 20, 1257-1261.
251. Thomsen, S.B., Rathcke, C.N., Zerahn, B., and Vestergaard, H. (2010) 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., 9, 86.
252. Ueland, T., Dahl, C.P., Gullestad, L., Aakhus, S., Broch, K., Skårdal, R., Vermeer, C., Aukrust, P., and Schurgers, L.J. (2011) Circulating levels of nonphosphorylated undercarboxylated matrix Gla protein are associated with disease severity in patients with chronic heart failure. Clin. Sci., 121, 119-127.
253. van den Heuvel, E.G., van Schoor, N.M., Lips, P., Magdeleyns, E.J., Deeg, D.J., Vermeer, C., and den Heijer, M. (2014) Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk factor of cardiovascular disease. Maturitas, 77, 137-141.
254. Schurgers, L.J., Cranenburg, E.C., and Vermeer, C. (2008) Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb. Haemost., 100, 593-603.
255. Mayer, O., Seidlerová, J., Bruthans, J., Filipovsky, J., Timoracká, K., Vaněk, J., Černá, L., Wohlfahrt, P., Cífková, R., Theuwissen, E., and Vermeer, C. (2014) Desphospho-uncarboxylated matrix glaprotein is associated with mortality risk in patients with chronic stable vascular disease. Atherosclerosis, 235, 162-168.
256. Schurgers, L.J., Barreto, D.V., Barreto, F.C. et al. (2010) 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., 5, 568-575.
257. Vassalle, C. and Iervasi, G. (2014) New insights for Matrix Gla Protein, vascular calcification and cardiovascular risk and outcome. Atherosclerosis, 235, 236-238.
258. Mani, A., Radhakrishnan, J., Wang, H., Mani, A., Mani, M.A., Nelson-Williams, C., Carew, K.S., Mane, S., Najmabadi, H., Wu, D., and Lifton, R.P. (2007) LRP6 mutation in a family with early coronary disease and metabolic risk factors. Science, 2 (315), 1278-1282.
259. Grant, S.F., Thorleifsson, G., Reynisdottir, I., Benediktsson, R., Manolescu, A., Sainz, J., Helgason, A., Stefansson, H., Emilsson, V., Helgadottir, A., Styrkarsdottir, U., Magnusson, K.P., Walters, G.B., Palsdottir, E., Jonsdottir, T., Gudmundsdottir, T., Gylfason, A., Saemundsdottir, J., Wilensky, R.L., Reilly, M.P., Rader, D.J., Bagger, Y., Christiansen, C., Gudnason, V., Sigurdsson, G., Thorsteinsdottir, U., Gulcher, J.R., Kong, A., and Stefansson, K. (2006) Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat. Genet., 38, 320-323.
260. Brandstrom, H., Stiger, F., Lind, L., Kahan, T., Melhus, H., and Kindmark, A. (2002) A single nucleotide polymorphism in the promoter region of the human gene for osteoprotegerin is related to vascular morphology and function. Biochem. Biophys. Res. Commun., 293, 13-17.
261. Soufi, M., Schoppet, M., Sattler, A.M., Herzum, M., Maisch, B., Hofbauer, L.C., and Schaefer, J.R. (2004) Osteoprotegerin gene polymorphisms in men with coronary artery disease. J. Clin. Endocrinol. Metab., 89, 3764-3768.
262. Ohmori, R., Momiyama, Y., Taniguchi, H., Tanaka, N., Kato, R., Nakamura, H., Ohsuzu, F., Nagano, M., and Egashira, T. (2006) Association between osteoprotegerin gene polymorphism and coronary artery disease in Japanese men. Atherosclerosis, 187, 215-217.
263. Rhee, E.J., Oh, K.W., Jung, C.H., Lee, W.Y., Oh, E.S., Yun, E.J., Baek, K.H., Kang, M.I., and Kim, S.W. (2006) The relationship between four single nucleotide polymorphisms in the promoter region of the osteoprotegerin gene and aortic calcification or coronary artery disease in Koreans. Clin. Endocrinol. (Oxford), 64, 689-697.
264. Straface, G., Biscetti, F., Pitocco, D., Bertoletti, G., Misuraca, M., Vincenzoni, C., Snider, F., Arena, V., Stigliano, E., Angelini, F., Iuliano, L., Boccia, S., deWaure, C., Giacchi, F., Ghirlanda, G., and Flex, A. (2011) Assessment of the genetic effects of polymorphisms in the osteoprotegerin gene, TNFRSF11B, on serum osteoprotegerin levels and carotid plaque vulnerability. Stroke, 42, 3022-3028.
265. Biscetti, F., Straface, G., Giovannini, S., Santoliquido, A., Angelini, F., Santoro, L., Porreca, C.F., Pecorini, G., Ghirlanda, G., and Flex, A. (2013) Association between TNFRSF11B gene polymorphisms and history of ischemic stroke in Italian diabetic patients. Hum. Genet., 132, 49-55.
266. Guo, C., Hu, F., Zhang, S., Wang, Y., and Liu, H. (2013) Association between osteoprotegerin gene polymorphisms and cardiovascular disease in type 2 diabetic patients. Genet. Mol. Biol., 36, 177-182.
267. Strand, M., Soderstrom, I., Wiklund, P.G., Hallmans, G., Weinehall, L., Soderberg, S., and Olsson, T. (2007) Polymorphisms at the osteoprotegerin and interleukin- 6 genes in relation to first-ever stroke. Cerebrovasc. Dis., 24, 418-425.
268. Tuñón-Le Poultel, D., Cannata-Andía, J.B., Román-García, P., Díaz-López, J.B., Coto, E., Gómez, C., Naves-Díaz, M., and Rodríguez, I. (2014) Association of matrix Gla protein gene functional polymorphisms with loss of bone mineral density and progression of aortic calcification. Osteoporos. Int., 25, 1237-1246.
269. Cassidy-Bushrow, A.E., Bielak, L.F., Levin, A.M., Sheedy, P.F. II, Turner, S.T., Boerwinkle, E., Lin, X., Kardia, S.L., and Peyser, P.A. (2013) Matrix gla protein gene polymorphism is associated with increased coronary artery calcification progression. Arterioscler. Thromb. Vasc. Biol., 33, 645-651.
270. Wang, Y., Chen, J., Zhang, Y., Yu, W., Zhang, C., Gong, L., Shao, L., Lu, J., Gao, Y., Chen, X., Chen, X., and Hui, R. (2013) 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., 6, 271-278.
271. Taylor, B.C., Schreiner, P.J., Doherty, T.M., Fornage, M., Carr, J.J., and Sidney, S. (2005) Matrix Gla protein and osteopontin genetic associations with coronary artery calcification and bone density: the CARDIA study. Hum. Genet., 116, 525-528.
272. Brenner, D., Labreuche, J., Touboul, P.J., Schmidt-Petersen, K., Poirier, O., Perret, C., Schönfelder, J., Combadière, C., Lathrop, M., Cambien, F., Brand-Herrmann, S.M., Amarenco, P., and GENIC Investigators (2006) Cytokine polymorphisms associated with carotid intima-media thickness in stroke patients. Stroke, 37, 1691-1696.
273. Schmidt-Petersen, K., Brand, E., Kim, Y., and Lee, C. (2008) Haplotype analysis revealed a genetic influence of osteopontin on large artery atherosclerosis. J. Biomed. Sci., 15, 529-533.
274. Telgmann, R., Nicaud, V., Hagedorn, C., Labreuche, J., Dördelmann, C., Elbaz, A., Gautier-Bertrand, M., Fischer, J.W., Evans, A., Morrison, C., Arveiler, D., Stoll, M., Amarenco, P., Cambien, F., Paul, M., and Brand-Herrmann, S.M. (2009) Osteopontin gene variation and cardio/cerebrovascular disease phenotypes. Atherosclerosis, 206, 209-215.
275. Falcini, F., Rigante, D., Masi, L., Covino, M., Franceschelli, F., Leoncini, G., Tarantino, G., Matucci Cerinic, M., and Brandi, M.L. (2013) Fibroblast growth factor 23 (FGF23) gene polymorphism in children with Kawasaki syndrome (KS) and susceptibility to cardiac abnormalities. Ital. J. Pediatr., 39, 69.
276. Chou, C.H., Wu, C.C., Song, I.W., Chuang, H.P., Lu, L.S., Chang, J.H., Kuo, S.Y., Lee, C.H., Wu, J.Y., Chen, Y.T., Kraus, V.B., and Lee, M.T. (2013) Genome-wide expression profiles of subchondral bone in osteoarthritis. Arthritis Res. Ther., 15, R190.
277. Conway, S.J., Izuhara, K., Kudo, Y., Litvin, J., Markwald, R., Ouyang, G., Arron, J.R., Holweg, C.T., and Kudo, A. (2014) The role of periostin in tissue remodeling across health and disease. Cell. Mol. Life Sci., 71, 1279-1288.
278. Chai, S.B., Sun, F., Nie, X.L., and Wang, J. (2014) Leptin and coronary heart disease: a systematic review and metaanalysis. Atherosclerosis, 233, 3-10.
279. Van Schooten, F.J., Hirvonen, A., Maas, L.M., De Mol, B.A., Kleinjans, J.C., Bell, D.A., and Durrer, J.D. (1998) Putative susceptibility markers of coronary artery disease: association between VDR genotype, smoking and aromatic DNA adduct levels in human right atrial tissue. FASEB J., 12, 1409-1417.
280. Ortlepp, J.R., Lauscher, J., Hoffmann, R., Hanrath, P., and Joost, H.G. (2001) The vitamin D receptor gene determines prevalence of non insulin dependent diabetes mellitus and coronary artery disease. Diabet. Med., 18, 842-845.
281. Ortlepp, J.R., von Korff, A., Hanrath, P., Zerres, K., and Hoffmann, R. (2003) Vitamin D receptor gene polymorphism BsmI is not associated with the prevalence and severity of CAD in a large-scale angiographic cohort of patients. Eur. J. Clin. Invest., 33, 106-109.
282. Kammerer, C.M., Dualan, A.A., Samollow, P.B., Périssé, A.R., Bauer, R.L., MacCluer, J.W., O'Leary, D.H., and Mitchell, B.D. (2004) Bone mineral density, carotid artery intimal medial thickness, and the vitamin D receptor BsmI polymorphism in Mexican American women. Calcif. Tissue Int., 75, 292-298.
283. El-Shehaby, A.M., El-Khatib, M.M., Marzouk, S., and Battah, A.A. (2013) Relationship of BsmI polymorphism of vitamin D receptor gene with left ventricular hypertrophy and atherosclerosis in hemodialysis patients. Scand. J. Clin. Lab. Invest., 73, 75-81.
284. Monraats, P.S., Fang, Y., Pons, D., Pires, N.M., Pols, H.A., Zwinderman, A.H., de Maat, M.P., Doevendans, P.A., DeWinter, R.J., Tio, R.A., Waltenberger, J., Frants, R.R., Quax, P.H., van der Laarse, A., van der Wall, E.E., Uitterlinden, A.G., and Jukema, J.W. (2010) Vitamin D receptor: a new risk marker for clinical restenosis after percutaneous coronary intervention. Expert Opin. Ther. Targets, 14, 243-251.
285. Ferrarezi, D.A., Bellili-Muñoz, N., Dubois-Laforgue, D., Cheurfa, N., Lamri, A., Reis, A.F., Le Feuvre, C., Roussel, R., Fumeron, F., Timsit, J., Marre, M., and Velho, G. (2013) Allelic variations of the vitamin D receptor (VDR) gene are associated with increased risk of coronary artery disease in type 2 diabetics: the DIABHYCAR prospective study. Diabetes Metab., 39, 263-270.
286. Malik, S., Fu, L., Juras, D.J., Karmali, M., Wong, B.Y., Gozdzik, A., and Cole, D.E. (2013) Common variants of the vitamin D binding protein gene and adverse health outcomes. Crit. Rev. Clin. Lab. Sci., 50, 1-22.