Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1998-2003
doi: 10.1161/hq1201.100229
doi: 10.1161/hq1201.100229
© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Differential Expression of Bone Matrix Regulatory Proteins in Human Atherosclerotic Plaques
From the Departments of Pathology (C.R.D., J.P.M.C., E.L., K.B.J.M.C., M.J.A.P.D.), Vascular Surgery (P.J.E.H.M.K., J.H.M.T.), and Biochemistry (H.M.H.S., C.V.), Cardiovascular Research Institute Maastricht, University of Maastricht, and Department of Rheumatology (P.P.M.G.), University Hospital Maastricht, Maastricht, Netherlands.
Correspondence to M.J.A.P. Daemen, MD, PhD, Department of Pathology, CARIM, University of Maastricht, PO Box 616, 6200 MD Maastricht, Netherlands. E-mail MDA{at}lpat.azm.nl
In the present study, we examined the expression of regulators of bone formation and osteoclastogenesis in human atherosclerosis because accumulating evidence suggests that atherosclerotic calcification shares features with bone calcification. The most striking finding of this study was the constitutive immunoreactivity of matrix Gla protein, osteocalcin, and bone sialoprotein in nondiseased aortas and the absence of bone morphogenetic protein (BMP)-2, BMP-4, osteopontin, and osteonectin in nondiseased aortas and early atherosclerotic lesions. When atherosclerotic plaques demonstrated calcification or bone formation, BMP-2, BMP-4, osteopontin, and osteonectin were upregulated. Interestingly, this upregulation was associated with a sustained immunoreactivity of matrix Gla protein, osteocalcin, and bone sialoprotein. The 2 modulators of osteoclastogenesis (osteoprotegerin [OPG] and its ligand, OPGL) were present in the nondiseased vessel wall and in early atherosclerotic lesions. In advanced calcified lesions, OPG was present in bone structures, whereas OPGL was only present in the extracellular matrix surrounding calcium deposits. The observed expression patterns suggest a tight regulation of the expression of bone matrix regulatory proteins during human atherogenesis. The expression pattern of both OPG and OPGL during atherogenesis might suggest a regulatory role of these proteins not only in osteoclastogenesis but also in atherosclerotic calcification.
Key Words: bone matrix proteins • atherosclerosis • vascular calcification • osteogenesis • osteoclastogenesis
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L. J. Schurgers, H. Aebert, C. Vermeer, B. Bultmann, and J. Janzen Oral anticoagulant treatment: friend or foe in cardiovascular disease? Blood, November 15, 2004; 104(10): 3231 - 3232. [Abstract] [Full Text] [PDF]
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S. M. Moe and N. X. Chen Pathophysiology of Vascular Calcification in Chronic Kidney Disease Circ. Res., September 17, 2004; 95(6): 560 - 567. [Abstract] [Full Text] [PDF]
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M. Soufi, M. Schoppet, A. M. Sattler, M. Herzum, B. Maisch, L. C. Hofbauer, and J. R. Schaefer Osteoprotegerin Gene Polymorphisms in Men with Coronary Artery Disease J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3764 - 3768. [Abstract] [Full Text] [PDF]
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M. Schoppet, N. Al-Fakhri, F. E. Franke, N. Katz, P. J. Barth, B. Maisch, K. T. Preissner, and L. C. Hofbauer Localization of Osteoprotegerin, Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand, and Receptor Activator of Nuclear Factor-{kappa}B Ligand in Monckeberg's Sclerosis and Atherosclerosis J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4104 - 4112. [Abstract] [Full Text] [PDF]
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K. Nitta, T. Akiba, K. Uchida, S. Otsubo, T. Takei, W. Yumura, T. Kabaya, and H. Nihei Serum osteoprotegerin levels and the extent of vascular calcification in haemodialysis patients Nephrol. Dial. Transplant., July 1, 2004; 19(7): 1886 - 1889. [Abstract] [Full Text] [PDF]
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M. Abedin, Y. Tintut, and L. L. Demer Vascular Calcification: Mechanisms and Clinical Ramifications Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1161 - 1170. [Abstract] [Full Text] [PDF]
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S. Kiechl, G. Schett, G. Wenning, K. Redlich, M. Oberhollenzer, A. Mayr, P. Santer, J. Smolen, W. Poewe, and J. Willeit Osteoprotegerin Is a Risk Factor for Progressive Atherosclerosis and Cardiovascular Disease Circulation, May 11, 2004; 109(18): 2175 - 2180. [Abstract] [Full Text] [PDF]
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A. Mazzone, M. C. Epistolato, R. De Caterina, S. Storti, S. Vittorini, S. Sbrana, J. Gianetti, S. Bevilacqua, M. Glauber, A. Biagini, et al. Neoangiogenesis, T-lymphocyte infiltration, and heat shock protein-60 are biological hallmarks of an immunomediated inflammatory process in end-stage calcified aortic valve stenosis J. Am. Coll. Cardiol., May 5, 2004; 43(9): 1670 - 1676. [Abstract] [Full Text] [PDF]
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D. J. Grainger Transforming Growth Factor {beta} and Atherosclerosis: So Far, So Good for the Protective Cytokine Hypothesis Arterioscler Thromb Vasc Biol, March 1, 2004; 24(3): 399 - 404. [Abstract] [Full Text]
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G. P. Sorescu, M. Sykes, D. Weiss, M. O. Platt, A. Saha, J. Hwang, N. Boyd, Y. C. Boo, J. D. Vega, W. R. Taylor, et al. Bone Morphogenic Protein 4 Produced in Endothelial Cells by Oscillatory Shear Stress Stimulates an Inflammatory Response J. Biol. Chem., August 15, 2003; 278(33): 31128 - 31135. [Abstract] [Full Text] [PDF]
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M. Schoppet, J. R. Schaefer, L. C. Hofbauer, S. Jono, K. Mori, Y. Nishizawa, A. Shioi, T. Miki, Y. Ikari, and K. Hara Low Serum Levels of Soluble RANK Ligand Are Associated With the Presence of Coronary Artery Disease in Men * Response Circulation, March 25, 2003; 107 (11): e76 - e76. [Full Text] [PDF]
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M. Schoppet, A. M. Sattler, J. R. Schaefer, M. Herzum, B. Maisch, and L. C. Hofbauer Increased Osteoprotegerin Serum Levels in Men with Coronary Artery Disease J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1024 - 1028. [Abstract] [Full Text] [PDF]
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K. L. Tyson, J. L. Reynolds, R. McNair, Q. Zhang, P. L. Weissberg, and C. M. Shanahan Osteo/Chondrocytic Transcription Factors and Their Target Genes Exhibit Distinct Patterns of Expression in Human Arterial Calcification Arterioscler Thromb Vasc Biol, March 1, 2003; 23(3): 489 - 494. [Abstract] [Full Text] [PDF]
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S. Jono, Y. Ikari, A. Shioi, K. Mori, T. Miki, K. Hara, and Y. Nishizawa Serum Osteoprotegerin Levels Are Associated With the Presence and Severity of Coronary Artery Disease Circulation, September 3, 2002; 106(10): 1192 - 1194. [Abstract] [Full Text] [PDF]
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M. Schoppet, K. T. Preissner, and L. C. Hofbauer RANK Ligand and Osteoprotegerin: Paracrine Regulators of Bone Metabolism and Vascular Function Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 549 - 553. [Abstract] [Full Text] [PDF]
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