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Cellular and Molecular Bioengineering

, Volume 5, Issue 3, pp 254–265 | Cite as

Gene Expression and Collagen Fiber Micromechanical Interactions of the Semilunar Heart Valve Interstitial Cell

  • Christopher A. Carruthers
  • Christina M. Alfieri
  • Erinn M. Joyce
  • Simon C. Watkins
  • Katherine E. Yutzey
  • Michael S. SacksEmail author
Article

Abstract

The semilunar (aortic and pulmonary) heart valves function under dramatically different hemodynamic environments, and have been shown to exhibit differences in mechanical properties, extracellular matrix (ECM) structure, and valve interstitial cell (VIC) biosynthetic activity. However, the relationship between VIC function and the unique micromechanical environment in each semilunar heart valve remains unclear. In the present study, we quantitatively compared porcine semilunar mRNA expression of primary ECM constituents, and layer- and valve-specific VIC–collagen mechanical interactions under increasing transvalvular pressure (TVP). Results indicated that the aortic valve (AV) had a higher fibrillar collagen mRNA expression level compared to the pulmonary valve (PV). We further noted that VICs exhibited larger deformations with increasing TVP in the collagen rich fibrosa layer, with substantially smaller changes in the spongiosa and ventricularis layers. While the VIC–collagen micromechanical coupling varied considerably between the semilunar valves, we observed that the VIC deformations in the fibrosa layer were similar at each valve’s respective peak TVP. This result suggests that each semilunar heart valve’s collagen fiber microstructure is organized to induce a consistent VIC deformation under its respective diastolic TVP. Collectively, our results are consistent with higher collagen biosynthetic demands for the AV compared to the PV, and that the valvular collagen microenvironment may play a significant role in regulating VIC function.

Keywords

Valve morphology Extracellular matrix Microstructure Cellular deformations Mechanobiology Heart valve remodeling Tissue engineered heart valve 

Notes

Acknowledgments

We thank Greg Gibson for training and assistance on the multi-photon microscope. Funding for this work was provided by NIH Grants R01 HL068816, R01 HL089750, and U54 RR022241. Christopher Carruthers was partially supported by NIH T32 EB003392 and a National Science Foundation Graduate Research Fellowship.

References

  1. 1.
    Aikawa, E., P. Whittaker, M. Farber, K. Mendelson, R. F. Padera, M. Aikawa, and F. J. Schoen. Human semilunar cardiac valve remodeling by activated cells from fetus to adult: implications for postnatal adaptation, pathology, and tissue engineering. Circulation 113:1344–1352, 2006.CrossRefGoogle Scholar
  2. 2.
    Aldous, I., J. Lee, and S. Wells. Differential changes in the molecular stability of collagen from the pulmonary and aortic valves during the fetal-to-neonatal transition. Ann. Biomed. Eng. 38:3000–3009, 2010.CrossRefGoogle Scholar
  3. 3.
    Aldous, I. G., S. P. Veres, A. Jahangir, and J. M. Lee. Differences in collagen cross-linking between the four valves of the bovine heart: a possible role in adaptation to mechanical fatigue. Am. J. Physiol. Heart Circ. Physiol. 296:H1898–H1906, 2009.CrossRefGoogle Scholar
  4. 4.
    Bouchard-Martel, J., E. Roussel, M. Drolet, M. Arsenault, and J. Couet. Interstitial cells from left-sided heart valves display more calcification potential than from right-sided valves: an in vitro study of porcine valves. J. Heart Valve Dis. 18:421–428, 2009.Google Scholar
  5. 5.
    Chakraborty, S., J. Cheek, B. Sakthivel, B. J. Aronow, and K. E. Yutzey. Shared gene expression profiles in developing heart valves and osteoblast progenitor cells. Physiol. Genomics 35:75–85, 2008.CrossRefGoogle Scholar
  6. 6.
    Christie, G. W., and B. G. Barratt-Boyes. Mechanical properties of porcine pulmonary valve leaflets: how do they differ from aortic leaflets? Ann. Thorac. Surg. 60:S195–S199, 1995.CrossRefGoogle Scholar
  7. 7.
    Hinton, Jr., R. B., J. Lincoln, G. H. Deutsch, H. Osinska, P. B. Manning, D. W. Benson, and K. E. Yutzey. Extracellular matrix remodeling and organization in developing and diseased aortic valves. Circ. Res. 98:1431–1438, 2006.CrossRefGoogle Scholar
  8. 8.
    Hoffman, B. D., and J. C. Crocker. Cell mechanics: dissecting the physical responses of cells to force. Annu. Rev. Biomed. Eng. 11:259–288, 2009.CrossRefGoogle Scholar
  9. 9.
    Huang, H. Y., J. Liao, and M. S. Sacks. In situ deformation of the aortic valve interstitial cell nucleus under diastolic loading. J. Biomech. Eng. 129:880–889, 2007.CrossRefGoogle Scholar
  10. 10.
    Ikhumetse, J., S. Konduri, J. Warnok, Y. Xing, and A. Yoganathan. Cyclic aortic pressure affects the biological properties of porcine pulmonary valve leaflets. J. Heart Valve Dis. 15:295–302, 2006.Google Scholar
  11. 11.
    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. 87:1240–1249, 2009.CrossRefGoogle Scholar
  12. 12.
    Kadner, A., O. Raisky, A. Degandt, D. Tamisier, D. Bonnet, D. Sidi, and P. R. Vouhe. The Ross procedure in infants and young children. Ann. Thorac. Surg. 85:803–808, 2008.CrossRefGoogle Scholar
  13. 13.
    Latif, N., P. Sarathchandra, P. M. Taylor, J. Antoniw, and M. H. Yacoub. Localization and pattern of expression of extracellular matrix components in human heart valves. J. Heart Valve Dis. 14:218–227, 2005.Google Scholar
  14. 14.
    Lincoln, J., C. M. Alfieri, and K. E. Yutzey. Development of heart valve leaflets and supporting apparatus in chicken and mouse embryos. Dev. Dyn. 230:239–250, 2004.CrossRefGoogle Scholar
  15. 15.
    Merryman, W. D., H. D. Lukoff, R. A. Long, G. C. Engelmayr, Jr., R. A. Hopkins, and M. S. Sacks. Synergistic effects of cyclic tension and transforming growth factor-beta1 on the aortic valve myofibroblast. Cardiovasc. Pathol. 16:268–276, 2007.CrossRefGoogle Scholar
  16. 16.
    Merryman, W. D., I. Youn, H. D. Lukoff, P. M. Krueger, F. Guilak, R. A. Hopkins, and M. S. Sacks. Correlation between heart valve interstitial cell stiffness and transvalvular pressure: implications for collagen biosynthesis. Am. J. Physiol. Heart Circ. Physiol. 290:H224–H231, 2006.CrossRefGoogle Scholar
  17. 17.
    Mirnajafi, A., J. M. Raymer, L. R. McClure, and M. S. Sacks. The flexural rigidity of the aortic valve leaflet in the commissural region. J. Biomech. 39:2966–2973, 2006.CrossRefGoogle Scholar
  18. 18.
    Mirnajafi, A., J. M. Raymer, M. J. Scott, and M. S. Sacks. The effects of collagen fiber orientation on the flexural properties of pericardial heterograft biomaterials. Biomaterials 26:795–804, 2005.CrossRefGoogle Scholar
  19. 19.
    Rabkin-Aikawa, E., M. Aikawa, M. Farber, J. R. Kratz, G. Garcia-Cardena, N. T. Kouchoukos, M. B. Mitchell, R. A. Jonas, and F. J. Schoen. Clinical pulmonary autograft valves: pathologic evidence of adaptive remodeling in the aortic site. J. Thorac. Cardiovasc. Surg. 128:552–561, 2004.CrossRefGoogle Scholar
  20. 20.
    Rabkin-Aikawa, E., M. Farber, M. Aikawa, and F. J. Schoen. Dynamic and reversible changes of interstitial cell phenotype during remodeling of cardiac valves. J. Heart Valve Dis. 13:841–847, 2004.Google Scholar
  21. 21.
    Sacks, M. S., W. David Merryman, and D. E. Schmidt. On the biomechanics of heart valve function. J. Biomech. 42:1804–1824, 2009.CrossRefGoogle Scholar
  22. 22.
    Screen, H. R., D. A. Lee, D. L. Bader, and J. C. Shelton. Development of a technique to determine strains in tendons using the cell nuclei. Biorheology 40:361–368, 2003.Google Scholar
  23. 23.
    Snider, P., R. B. Hinton, R. A. Moreno-Rodriguez, J. Wang, R. Rogers, A. Lindsley, F. Li, D. A. Ingram, D. Menick, L. Field, A. B. Firulli, J. D. Molkentin, R. Markwald, and S. J. Conway. Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart. Circ. Res. 102:752–760, 2008.CrossRefGoogle Scholar
  24. 24.
    Stella, J. A., J. Liao, Y. Hong, W. David Merryman, W. R. Wagner, and M. S. Sacks. Tissue-to-cellular level deformation coupling in cell micro-integrated elastomeric scaffolds. Biomaterials 29:3228–3236, 2008.CrossRefGoogle Scholar
  25. 25.
    Stella, J. A., and M. S. Sacks. On the biaxial mechanical properties of the layers of the aortic valve leaflet. J. Biomech. Eng. 129:757–766, 2007.CrossRefGoogle Scholar
  26. 26.
    Stephens, E., C. Durst, J. Swanson, K. Grande-Allen, N. Ingels, and D. Miller. Functional coupling of valvular interstitial cells and collagen via α2β1 integrins in the mitral leaflet. Cell. Mol. Bioeng. 3:428–437, 2010.CrossRefGoogle Scholar
  27. 27.
    Stephens, E., and K. Grande-Allen. Age-related changes in collagen synthesis and turnover in porcine heart valves. J. Heart Valve Dis. 16:672–682, 2007.Google Scholar
  28. 28.
    Taylor, P. M., P. Batten, N. J. Brand, P. S. Thomas, and M. H. Yacoub. The cardiac valve interstitial cell. Int. J. Biochem. Cell Biol. 35:113–118, 2003.CrossRefGoogle Scholar
  29. 29.
    Watkins, S. Immunohistochemistry. In: Current Protocols in Cytometry. New York: John Wiley & Sons, Inc., 2001.Google Scholar

Copyright information

© Biomedical Engineering Society 2012

Authors and Affiliations

  • Christopher A. Carruthers
    • 1
  • Christina M. Alfieri
    • 2
  • Erinn M. Joyce
    • 1
  • Simon C. Watkins
    • 3
  • Katherine E. Yutzey
    • 2
  • Michael S. Sacks
    • 4
    Email author
  1. 1.Department of BioengineeringUniversity of PittsburghPittsburghUSA
  2. 2.Division of Molecular Cardiovascular BiologyCincinnati Children’s Medical CenterCincinnatiUSA
  3. 3.Department of Cell Biology and PhysiologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  4. 4.Department of Biomedical Engineering, Institute for Computational Engineering and SciencesThe University of Texas at AustinAustinUSA

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