on April 28, 2003
Circulation. 2003
Published online before print April 28, 2003, doi: 10.1161/01.CIR.0000070591.21548.69
Published online before print April 28, 2003, doi: 10.1161/01.CIR.0000070591.21548.69
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Submitted on December 31, 2002
From the Divisions of Cardiology and Cardiothoracic Surgery (N.M.R., D.A.F., R.O.B.), Northwestern University Feinberg School of Medicine, and Institute for Bioengineering and Nanoscience in Advanced Medicine (S.R.S.), Northwestern University, Chicago, Ill, and Department of Molecular Biology and Biochemistry (M.S., D.R., T.S.), Department of Cardiology and Cardiothoracic Surgery (J.D., T.O., A.J.T.), and Electron Microscopy Laboratory (M.S.), Mayo Clinic, Rochester, Minn. * To whom correspondence should be addressed. E-mail: n.rajamannan{at}northwestern.edu.
Background--Calcific aortic stenosis is the third most common cardiovascular disease in the United States. We hypothesized that the mechanism for aortic valve calcification is similar to skeletal bone formation and that this process is mediated by an osteoblast-like phenotype. Methods and Results--To test this hypothesis, we examined calcified human aortic valves replaced at surgery (n=22) and normal human valves (n=20) removed at time of cardiac transplantation. Contact microradiography and micro-computerized tomography were used to assess the 2-dimensional and 3-dimensional extent of mineralization. Mineralization borders were identified with von Kossa and Goldner's stains. Electron microscopy and energy-dispersive spectroscopy were performed for identification of bone ultrastructure and CaPO4 composition. To analyze for the osteoblast and bone markers, reverse transcriptase-polymerase chain reaction was performed on calcified versus normal human valves for osteopontin, bone sialoprotein, osteocalcin, alkaline phosphatase, and the osteoblast-specific transcription factor Cbfa1. Microradiography and micro-computerized tomography confirmed the presence of calcification in the valve. Special stains for hydroxyapatite and CaPO4 were positive in calcification margins. Electron microscopy identified mineralization, whereas energy-dispersive spectroscopy confirmed the presence of elemental CaPO4. Reverse transcriptase-polymerase chain reaction revealed increased mRNA levels of osteopontin, bone sialoprotein, osteocalcin, and Cbfa1 in the calcified valves. There was no change in alkaline phosphatase mRNA level but an increase in the protein expression in the diseased valves. Conclusions--These findings support the concept that aortic valve calcification is not a random degenerative process but an active regulated process associated with an osteoblast-like phenotype.
Revised on March 20, 2003
Accepted on March 21, 2003
Human Aortic Valve Calcification Is Associated With an Osteoblast Phenotype
Nalini M. Rajamannan MD*,
Key words: valves • stenosis • calcium
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|
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|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
V. Liebe, M. Brueckmann, M. Borggrefe, and J. J. Kaden Statin therapy of calcific aortic stenosis: hype or hope? Eur. Heart J., April 1, 2006; 27(7): 773 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D Skowasch, S Schrempf, C J Preusse, J A Likungu, A Welz, B Luderitz, and G Bauriedel Tissue resident C reactive protein in degenerative aortic valves: correlation with serum C reactive protein concentrations and modification by statins Heart, April 1, 2006; 92(4): 495 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Lee, D. M. Basalyga, A. Simionescu, J. C. Isenburg, D. T. Simionescu, and N. R. Vyavahare Elastin Calcification in the Rat Subdermal Model Is Accompanied by Up-Regulation of Degradative and Osteogenic Cellular Responses Am. J. Pathol., February 1, 2006; 168(2): 490 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Butcher, S. Tressel, T. Johnson, D. Turner, G. Sorescu, H. Jo, and R. M. Nerem Transcriptional Profiles of Valvular and Vascular Endothelial Cells Reveal Phenotypic Differences: Influence of Shear Stress Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 69 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Skowasch, S. Schrempf, N. Wernert, M. Steinmetz, A. Jabs, I. Tuleta, U. Welsch, C. J. Preusse, J. A. Likungu, A. Welz, et al. Cells of primarily extravalvular origin in degenerative aortic valves and bioprostheses Eur. Heart J., December 1, 2005; 26(23): 2576 - 2580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 D. Hamerman Osteoporosis and atherosclerosis: biological linkages and the emergence of dual-purpose therapies QJM, July 1, 2005; 98(7): 467 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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N M Rajamannan, M Subramaniam, S R Stock, N J Stone, M Springett, K I Ignatiev, J P McConnell, R J Singh, R O Bonow, and T C Spelsberg Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve Heart, June 1, 2005; 91(6): 806 - 810. [Abstract] [Full Text] [PDF]
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G.D.M. Collett and A.E. Canfield Angiogenesis and Pericytes in the Initiation of Ectopic Calcification Circ. Res., May 13, 2005; 96(9): 930 - 938. [Abstract] [Full Text] [PDF]
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C. A. Simmons, G. R. Grant, E. Manduchi, and P. F. Davies Spatial Heterogeneity of Endothelial Phenotypes Correlates With Side-Specific Vulnerability to Calcification in Normal Porcine Aortic Valves Circ. Res., April 15, 2005; 96(7): 792 - 799. [Abstract] [Full Text] [PDF]
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D. A. Towler Inorganic Pyrophosphate: A Paracrine Regulator of Vascular Calcification and Smooth Muscle Phenotype Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 651 - 654. [Full Text] [PDF]
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Systolic murmur in an asymptomatic 70 year old man Heart, January 1, 2005; 91(1): 125 - 125. [Full Text] [PDF]
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M. Abedin, Y. Tintut, and L. L. Demer Mesenchymal Stem Cells and the Artery Wall Circ. Res., October 1, 2004; 95(7): 671 - 676. [Abstract] [Full Text] [PDF]
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N. M. Rajamannan and C. M. Otto Targeted Therapy to Prevent Progression of Calcific Aortic Stenosis Circulation, September 7, 2004; 110(10): 1180 - 1182. [Full Text] [PDF]
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D. Messika-Zeitoun, M.-C. Aubry, D. Detaint, L. F. Bielak, P. A. Peyser, P. F. Sheedy, S. T. Turner, J. F. Breen, C. Scott, A. J. Tajik, et al. Evaluation and Clinical Implications of Aortic Valve Calcification Measured by Electron-Beam Computed Tomography Circulation, July 20, 2004; 110(3): 356 - 362. [Abstract] [Full Text] [PDF]
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 R. Vattikuti and D. A. Towler Osteogenic regulation of vascular calcification: an early perspective Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E686 - E696. [Abstract] [Full Text] [PDF]
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S. H. Rahimtoola The year in valvular heart disease J. Am. Coll. Cardiol., February 4, 2004; 43(3): 491 - 504. [Full Text] [PDF]
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C. M. Otto Why is aortic sclerosis associated with adverse clinical outcomes? J. Am. Coll. Cardiol., January 21, 2004; 43(2): 176 - 178. [Full Text] [PDF]
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C. M. Grossman, N. M. Rajamannan, S. R. Stock, D. A. Fullerton, R. O. Bonow, M. Subramaniam, D. Rickard, J. Donovan, M. Springett, T. Orszulak, et al. Human Aortic Valve Calcification * Response Circulation, December 9, 2003; 108 (23): e163 - e163. [Full Text] [PDF]
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G. M. Novaro, R. Sachar, G. L. Pearce, D. L. Sprecher, and B. P. Griffin Association Between Apolipoprotein E Alleles and Calcific Valvular Heart Disease Circulation, October 14, 2003; 108(15): 1804 - 1808. [Abstract] [Full Text] [PDF]
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