The bicuspid aortic valve (AV) is the most common cardiac congenital anomaly and has been found to be a significant risk factor for developing calcific AV disease. However, the mechanisms of disease development remain unclear. In this study we quantified the structure of human normal and bicuspid leaflets in the early disease stage. From these individual leaflet maps average fiber structure maps were generated using a novel spline based technique. Interestingly, we found statistically different and consistent regional structures between the normal and bicuspid valves. The regularity in the observed microstructure was a surprising finding, especially for the pathological BAV leaflets and is an essential cornerstone of any predictive mathematical models of valve disease. In contrast, we determined that isolated valve interstitial cells from BAV leaflets show the same in vitro calcification pathways as those from the normal AV leaflets. This result suggests the VICs are not intrinsically different when isolated, and that external features, such as abnormal microstructure and altered flow may be the primary contributors in the accelerated calcification experienced by BAV patients.
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Similar content being viewed by others Explore related subjectsDiscover the latest articles and news from researchers in related subjects, suggested using machine learning. AbbreviationsAortic valve
Tricuspid aortic valve
Bicuspid aortic valve
Aortic stenosis
Aortic valve sclerosis
Calcific aortic valve disease
Valve interstitial cell
Aortic valve area
Extra cellular matrix
Small angle light scattering
Hematoxylin and Eosin
Modified Movat Pentachrome
Dulbecco’s modified Eagle’s medium
Smooth muscle actin
Glyceraldehyde 3-phosphate dehydrogenase
Root mean square distance
Magnetic resonance imaging
Orientation index
Aggarwal, A., V. S. Aguilar, C.-H. Lee, G. Ferrari, J. H. Gorman, R. C. Gorman, and M. S. Sacks. Functional Imaging and Modeling of the Heart, Springer, 2013, pp. 141–149.
Balachandran, K., P. Sucosky, and A. P. Yoganathan. Hemodynamics and mechanobiology of aortic valve inflammation and calcification. Int. J. Inflam. 2011:263870, 2011. doi:10.4061/2011/263870.
Bartels, R. H., J. C. Beatty, and B. A. Barsky. An Introduction to Splines for Use in Computer Graphics and Geometric Modeling. Los Altos, CA: Morgan Kaufmann, 1987.
Branchetti, E., R. Sainger, P. Poggio, J. B. Grau, J. Patterson-Fortin, J. E. Bavaria, M. Chorny, E. Lai, R. C. Gorman, R. J. Levy, and G. Ferrari. Antioxidant enzymes reduce DNA damage and early activation of valvular interstitial cells in aortic valve sclerosis. Arterioscler. Thromb. Vasc. Biol. 33(2):e66–e74, 2013.
De Sa, M. P., E. S. Bastos, and H. Murad. Bicuspid aortic valve: theoretical and clinical aspects of concomitant ascending aorta replacement. Rev. Bras. Cir. Cardiovasc. 24(2):218–224, 2009.
Evangelista, A. Bicuspid aortic valve and aortic root disease. Curr. Cardiol. Rep. 13(3):234–241, 2011.
Fedak, P. W., S. Verma, T. E. David, R. L. Leask, R. D. Weisel, and J. Butany. Clinical and pathophysiological implications of a bicuspid aortic valve. Circulation 106:900–904, 2002.
Friedman, T., A. Mani, and J. A. Elefteriades. Bicuspid aortic valve: clinical approach and scientific review of a common clinical entity. Expert Rev. Cardiovasc. Ther. 6(2):235–248, 2008.
Garg, V. Molecular genetics of aortic valve disease. Curr. Opin. Cardiol. 21(3):180–184, 2006.
Joyce, E. M., J. Liao, F. J. Schoen, J. E. Mayer, Jr., and M. S. Sacks. Functional collagen fiber architecture of the pulmonary heart valve cusp. Ann. Thorac. Surg. 87(4):1240–1249, 2009.
Lewin, M. B., and C. M. Otto. The bicuspid aortic valve: adverse outcomes from infancy to old age. Circulation 111(7):832–834, 2005.
Mardia, K. V. Statistics of Directional Data. New York: Academic Press, 1972.
Moran, P. A. Notes on continuous stochastic phenomena. Biometrika 37(1–2):17–23, 1950.
Paradis, E., J. Claude, and K. Strimmer. APE: Analyses of Phylogenetics and Evolution in R language. Bioinformatics 20(2):289–290, 2004.
Poggio, P., R. Sainger, E. Branchetti, J. B. Grau, E. K. Lai, R. C. Gorman, M. S. Sacks, A. Parolari, J. E. Bavaria, and G. Ferrari. Noggin attenuates the osteogenic activation of human valve interstitial cells in aortic valve sclerosis. Cardiovasc. Res. 98(3):402–410, 2013.
Roberts, W. C., and J. M. Ko. Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation. Circulation 111(7):920–925, 2005.
Robicsek, F., M. J. Thubrikar, J. W. Cook, and B. Fowler. The congenitally bicuspid aortic valve: how does it function? Why does it fail? Ann. Thorac. Surg. 77(1):177–185, 2004.
Rosenhek, R., T. Binder, G. Porenta, I. Lang, G. Christ, M. Schemper, G. Maurer, and H. Baumgartner. Predictors of outcome in severe, asymptomatic aortic stenosis. N. Engl. J. Med. 343(9):611–617, 2000.
Sacks, M. S., W. D. Merryman, and D. E. Schmidt. On the biomechanics of heart valve function. J. Biomech. 42(12):1804–1824, 2009.
Sacks, M. S., and F. J. Schoen. Collagen fiber disruption occurs independent of calcification in clinically explanted bioprosthetic heart valves. J. Biomed. Mater. Res. 62(3):359–371, 2002.
Sacks, M. S., D. B. Smith, and E. D. Hiester. A small angle light scattering device for planar connective tissue microstructural analysis. Ann. Biomed. Eng. 25(4):678–689, 1997.
Sainger, R., J. B. Grau, E. Branchetti, P. Poggio, W. F. Seefried, B. C. Field, M. A. Acker, R. C. Gorman, J. H. Gorman, 3rd, C. W. Hargrove, 3rd, J. E. Bavaria, and G. Ferrari. Human myxomatous mitral valve prolapse: role of bone morphogenetic protein 4 in valvular interstitial cell activation. J. Cell. Physiol. 227(6):2595–2604, 2012.
Schaefer, B. M., M. B. Lewin, K. K. Stout, E. Gill, A. Prueitt, P. H. Byers, and C. M. Otto. The bicuspid aortic valve: an integrated phenotypic classification of leaflet morphology and aortic root shape. Heart 94(12):1634–1638, 2008.
Siu, S. C., and C. K. Silversides. Bicuspid aortic valve disease. J. Am. Coll. Cardiol. 55(25):2789–2800, 2010.
Smith, D. B., M. S. Sacks, P. M. Pattany, and R. Schroeder. High-resolution magnetic resonance imaging to characterize the geometry of fatigued porcine bioprosthetic heart valves. J. Heart Valve Dis. 6(4):424–432, 1997.
Sun, L., S. Chandra, and P. Sucosky. Ex vivo evidence for the contribution of hemodynamic shear stress abnormalities to the early pathogenesis of calcific bicuspid aortic valve disease. PLoS ONE 7:e48843, 2012. doi:10.1371/journal.pone.0048843
Thornton, M. High Speed Dynamic, 3-D Surface Imaging. London, ON: Electrical Engineering, University of Western Ontario, 1996.
Towler, D. A. Molecular and cellular aspects of calcific aortic valve disease. Circ. Res. 113:198–208, 2013. doi:10.1161/CIRCRESAHA.113.300155.
Yip, C. Y., and C. A. Simmons. The aortic valve microenvironment and its role in calcific aortic valve disease. Cardiovasc. Pathol. 20(3):177–182, 2011.
This work was supported by the following sources—National Institute of Health (grant number grant numbers HL63954, HL103723 and HL73021 to R.C.G. and J.H.G.) and Moncrief Chair funds (M.S.S.). Help from Vanessa Aguilar in carrying out several of the experiments is greatly appreciated. American Heart Association Postdoctoral Fellowship Award 14POST18720037 to A.A.
Conflict of interestNone declared.
Author information Authors and AffiliationsCenter for Cardiovascular Simulation, Institute for Computational Engineering Sciences and the Department of Biomedical Engineering, The University of Texas at Austin, 201 East 24th Street, ACES 5.438, One University Station, C0200, Austin, TX, 78712-0027, USA
Ankush Aggarwal & Michael S. Sacks
Gorman Cardiovascular Research Group, University of Pennsylvania, Philadelphia, PA, USA
Giovanni Ferrari, Rachana Sainger, Joseph H. Gorman III & Robert Gorman
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
Erin Joyce
Division of Statistics & Scientific Computation and Department of Integrative Biology, University of Texas at Austin, Austin, TX, USA
Michael J. Daniels
Correspondence to Michael S. Sacks.
Additional informationAssociate Editor Jane Grande-Allen oversaw the review of this article.
Electronic supplementary materialBelow is the link to the electronic supplementary material.
About this article Cite this articleAggarwal, A., Ferrari, G., Joyce, E. et al. Architectural Trends in the Human Normal and Bicuspid Aortic Valve Leaflet and Its Relevance to Valve Disease. Ann Biomed Eng 42, 986–998 (2014). https://doi.org/10.1007/s10439-014-0973-0
Received: 30 September 2013
Accepted: 09 January 2014
Published: 01 February 2014
Issue Date: May 2014
DOI: https://doi.org/10.1007/s10439-014-0973-0
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