Skip to main content

Biological Mechanics of the Heart Valve Interstitial Cell

  • Chapter
  • First Online:
Advances in Heart Valve Biomechanics

Abstract

Heart valves are composed of multilayered tissues that contain a population of vascular endothelial cells (VEC) on the blood contacting surfaces and valve interstitial cells (VIC) in the bulk tissue mass that maintain homeostasis and respond to injury. The mechanosensitive nature of VICs facilitates the regulation of growth and remodeling of heart valve leaflets throughout different stages of life. However, pathological phenomenon such as mitral valve regurgitation and calcific aortic valve disease lead to pathological micromechanical environments. Such scenarios highlight the importance of studying the mechanobiology of VICs to better understand their mechanical and biosynthetic behavior. In the present chapter, we review use of novel experimental-computational techniques to link VIC biosynthetic response to changes in in vivo deformation in health and disease. In addition, we discuss the development of tissue-level models that shed light on the biomechanical state of VICs in situ. To conclude, we outline future directions for heart valve mechanobiology including model-driven experiments and highlight the need for high-fidelity, multi-scale models to link the cell-, tissue-, and organ-level events of heart valve growth and remodeling.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Merryman WD, Lukoff HD, Long RA, Engelmayr GC Jr, Hopkins RA, Sacks MS. Synergistic effects of cyclic tension and transforming growth factor-beta1 on the aortic valve myofibroblast. Cardiovasc Pathol. 2007;16(5):268–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Guyton AC. Textbook of medical physiology. 5th ed. Philadelphia: W.B. Saunders Company; 1976.

    Google Scholar 

  3. He Z, Ritchie J, Grashow JS, Sacks MS, Yoganathan AP. In vitro dynamic strain behavior of the mitral valve posterior leaflet. J Biomech Eng. 2005;127(3):504–11.

    Article  PubMed  Google Scholar 

  4. He Z, Sacks MS, Baijens L, Wanant S, Shah P, Yoganathan AP. Effects of papillary muscle position on in-vitro dynamic strain on the porcine mitral valve. J Heart Valve Dis. 2003;12(4):488–94.

    PubMed  Google Scholar 

  5. Sacks MS, Enomoto Y, Graybill JR, Merryman WD, Zeeshan A, Yoganathan AP, et al. In-vivo dynamic deformation of the mitral valve anterior leaflet. Ann Thorac Surg. 2006;82(4):1369–77.

    Article  PubMed  Google Scholar 

  6. Sacks MS, He Z, Baijens L, Wanant S, Shah P, Sugimoto H, et al. Surface strains in the anterior leaflet of the functioning mitral valve. Ann Biomed Eng. 2002;30(10):1281–90.

    Article  CAS  PubMed  Google Scholar 

  7. Ayoub S, Ferrari G, Gorman RC, Gorman JH, Schoen FJ, Sacks MS. Heart valve biomechanics and underlying mechanobiology. Compr Physiol. 2016;6(4):1743–80.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Sacks MS, Yoganathan AP. Heart valve function: a biomechanical perspective. Philos Trans R Soc Lond Ser B Biol Sci. 2007;362(1484):1369–91.

    Article  Google Scholar 

  9. Buchanan RM, Sacks MS. Interlayer micromechanics of the aortic heart valve leaflet. Biomech Model Mechanobiol. 2014;13(4):813–26.

    Article  PubMed  Google Scholar 

  10. Rego BV, Sacks MS. A functionally graded material model for the transmural stress distribution of the aortic valve leaflet. J Biomech. 2017;54:88–95.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Stella JA, Sacks MS. On the biaxial mechanical properties of the layers of the aortic valve leaflet. J Biomech Eng. 2007;129(5):757–66.

    Article  PubMed  Google Scholar 

  12. Rego BV, Wells SM, Lee CH, Sacks MS. Mitral valve leaflet remodelling during pregnancy: insights into cell-mediated recovery of tissue homeostasis. J R Soc Interface. 2016;13(125):20160709.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lee CH, Carruthers CA, Ayoub S, Gorman RC, Gorman JH 3rd, Sacks MS. Quantification and simulation of layer-specific mitral valve interstitial cells deformation under physiological loading. J Theor Biol. 2015;373:26–39.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Pierlot CM, Lee JM, Amini R, Sacks MS, Wells SM. Pregnancy-induced remodeling of collagen architecture and content in the mitral valve. Ann Biomed Eng. 2014;42(10):2058–71.

    Article  PubMed  Google Scholar 

  15. Pierlot CM, Moeller AD, Lee JM, Wells SM. Pregnancy-induced remodeling of heart valves. Am J Physiol Heart Circ Physiol. 2015;309(9):H1565–78.

    Article  CAS  PubMed  Google Scholar 

  16. Lam NT, Muldoon TJ, Quinn KP, Rajaram N, Balachandran K. Valve interstitial cell contractile strength and metabolic state are dependent on its shape. Integr Biol. 2016;8(10):1079–89.

    Article  CAS  Google Scholar 

  17. Tandon I, Razavi A, Ravishankar P, Walker A, Sturdivant NM, Lam NT, et al. Valve interstitial cell shape modulates cell contractility independent of cell phenotype. J Biomech. 2016;49(14):3289–97.

    Article  PubMed  Google Scholar 

  18. Ayoub S, Lee C-H, Driesbaugh KH, Anselmo W, Hughes CT, Ferrari G, et al. Regulation of valve interstitial cell homeostasis by mechanical deformation: implications for heart valve disease and surgical repair. J R Soc Interface. 2017;14:20170580.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lee CH, Zhang W, Feaver K, Gorman RC, Gorman JH 3rd, Sacks MS. On the in vivo function of the mitral heart valve leaflet: insights into tissue-interstitial cell biomechanical coupling. Biomech Model Mechanobiol. 2017;16:1613.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Rabkin E, Aikawa M, Stone JR, Fukumoto Y, Libby P, Schoen FJ. Activated interstitial myofibroblasts express catabolic enzymes and mediate matrix remodeling in myxomatous heart valves. Circulation. 2001;104(21):2525–32.

    Article  CAS  PubMed  Google Scholar 

  21. Rajamannan NM, Evans FJ, Aikawa E, Grande-Allen KJ, Demer LL, Heistad DD, et al. Calcific aortic valve disease: not simply a degenerative process: a review and agenda for research from the National Heart and Lung and Blood Institute Aortic Stenosis Working Group. Executive summary: calcific aortic valve disease-2011 update. Circulation. 2011;124(16):1783–91.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Sacks MS, Merryman WD, Schmidt DE. On the biomechanics of heart valve function. J Biomech. 2009;42(12):1804–24.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Carruthers CA, Good B, D’Amore A, Liao J, Amini R, Watkins SC, et al., editors. Alterations in the microstructure of the anterior mitral valve leaflet under physiological stress. In: ASME 2012 summer bioengineering conference. American Society of Mechanical Engineers; 2012.

    Google Scholar 

  24. Sakamoto Y, Buchanan RM, Sacks MS. On intrinsic stress fiber contractile forces in semilunar heart valve interstitial cells using a continuum mixture model. J Mech Behav Biomed Mater. 2016;54:244–58.

    Article  PubMed  Google Scholar 

  25. Sakamoto Y, Buchanan RM, Sanchez-Adams J, Guilak F, Sacks MS. On the functional role of valve interstitial cell stress fibers: a continuum modeling approach. J Biomech Eng. 2017;139(2):021007.

    Article  Google Scholar 

  26. Buchanan RM. An integrated computational-experimental approach for the in situ estimation of valve interstitial cell biomechanical state. Austin: The University of Texas at Austin; 2016.

    Google Scholar 

  27. Merryman WD, Youn I, Lukoff HD, Krueger PM, Guilak F, Hopkins RA, et al. Correlation between heart valve interstitial cell stiffness and transvalvular pressure: implications for collagen biosynthesis. Am J Physiol Heart Circ Physiol. 2006;290(1):H224–31.

    Article  CAS  PubMed  Google Scholar 

  28. Theret DP, Levesque MJ, Sato M, Nerem RM, Wheeler LT. The application of a homogeneous half-space model in the analysis of endothelial cell micropipette measurements. J Biomech Eng. 1988;110(3):190–9.

    Article  CAS  PubMed  Google Scholar 

  29. Rocnik EF, van der Veer E, Cao H, Hegele RA, Pickering JG. Functional linkage between the endoplasmic reticulum protein Hsp47 and procollagen expression in human vascular smooth muscle cells. J Biol Chem. 2002;277(41):38571–8.

    Article  CAS  PubMed  Google Scholar 

  30. Merryman WD, Liao J, Parekh A, Candiello JE, Lin H, Sacks MS. Differences in tissue-remodeling potential of aortic and pulmonary heart valve interstitial cells. Tissue Eng. 2007;13(9):2281–9.

    Article  PubMed  Google Scholar 

  31. Costa KD, Yin FC. Analysis of indentation: implications for measuring mechanical properties with atomic force microscopy. J Biomech Eng. 1999;121(5):462–71.

    Article  CAS  PubMed  Google Scholar 

  32. Mathur AB, Collinsworth AM, Reichert WM, Kraus WE, Truskey GA. Endothelial, cardiac muscle and skeletal muscle exhibit different viscous and elastic properties as determined by atomic force microscopy. J Biomech. 2001;34(12):1545–53.

    Article  CAS  PubMed  Google Scholar 

  33. Sato M, Theret DP, Wheeler LT, Ohshima N, Nerem RM. Application of the micropipette technique to the measurement of cultured porcine aortic endothelial cell viscoelastic properties. J Biomech Eng. 1990;112(3):263–8.

    Article  CAS  PubMed  Google Scholar 

  34. Guilak F, Ting-Beall HP, Baer AE, Trickey WR, Erickson GR, Setton LA. Viscoelastic properties of intervertebral disc cells. Identification of two biomechanically distinct cell populations. Spine. 1999;24(23):2475–83.

    Article  CAS  PubMed  Google Scholar 

  35. Na S, Sun Z, Meininger GA, Humphrey JD. On atomic force microscopy and the constitutive behavior of living cells. Biomech Model Mechanobiol. 2004;3(2):75–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Frisch-Fay R. Flexible bars. Washington, DC: Butterworths; 1962. 220 p.

    Google Scholar 

  37. Merryman WD, Huang HY, Schoen FJ, Sacks MS. The effects of cellular contraction on aortic valve leaflet flexural stiffness. J Biomech. 2006;39(1):88–96.

    Article  PubMed  Google Scholar 

  38. Mirnajafi A, Raymer J, Scott MJ, Sacks MS. The effects of collagen fiber orientation on the flexural properties of pericardial heterograft biomaterials. Biomaterials. 2005;26(7):795–804.

    Article  CAS  PubMed  Google Scholar 

  39. Mirnajafi A, Raymer JM, McClure LR, Sacks MS. The flexural rigidity of the aortic valve leaflet in the commissural region. J Biomech. 2006;39(16):2966–73.

    Article  PubMed  Google Scholar 

  40. Billiar KL, Sacks MS. Biaxial mechanical properties of the native and glutaraldehyde-treated aortic valve cusp: Part II—A structural constitutive model. J Biomech Eng. 2000;122(4):327–35.

    Article  CAS  PubMed  Google Scholar 

  41. Billiar KL, Sacks MS. Biaxial mechanical properties of the natural and glutaraldehyde treated aortic valve cusp—Part I: Experimental results. J Biomech Eng. 2000;122(1):23–30.

    Article  CAS  PubMed  Google Scholar 

  42. Mohri H, Reichenback D, Merendino K. Biology of homologous and heterologous aortic valves. In: Ionescu M, Ross D, Wooler G, editors. Biological tissue in heart valve replacement. London: Butterworths; 1972. p. 137.

    Google Scholar 

  43. Vesely I, Boughner D. Analysis of the bending behaviour of porcine xenograft leaflets and of natural aortic valve material: bending stiffness, neutral axis and shear measurements. J Biomech. 1989;22(6/7):655–71.

    Article  CAS  PubMed  Google Scholar 

  44. Song T, Vesely I, Boughner D. Effects of dynamic fixation on shear behavior of porcine xenograft valves. Biomaterials. 1990;11:191–6.

    Article  CAS  PubMed  Google Scholar 

  45. Lu SCH, Pister KS. Decomposition of deformation and representation of the free energy function for isotropic thermoelastic solids. Int J Solids Struct. 1975;11(7–8):927–34.

    Article  Google Scholar 

  46. Benton JA, Fairbanks BD, Anseth KS. Characterization of valvular interstitial cell function in three dimensional matrix metalloproteinase degradable PEG hydrogels. Biomaterials. 2009;30(34):6593–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Byrant SJ, Anseth KS. Photopolymerization of hydrogel scaffolds. In: Ma PX, Elisseeff J, editors. Scaffolding in tissue engineering. New York: CRC Press; 2005. p. 71–90.

    Chapter  Google Scholar 

  48. Balachandran K, Alford PW, Wylie-Sears J, Goss JA, Grosberg A, Bischoff J, et al. Cyclic strain induces dual-mode endothelial-mesenchymal transformation of the cardiac valve. Proc Natl Acad Sci U S A. 2011;108(50):19943–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Balachandran K, Hussain S, Yap CH, Padala M, Chester AH, Yoganathan AP. Elevated cyclic stretch and serotonin result in altered aortic valve remodeling via a mechanosensitive 5-HT(2A) receptor-dependent pathway. Cardiovasc Pathol. 2012;21(3):206–13.

    Article  CAS  PubMed  Google Scholar 

  50. Balachandran K, Konduri S, Sucosky P, Jo H, Yoganathan A. An ex vivo study of the biological properties of porcine aortic valves in response to circumferential cyclic stretch. Ann Biomed Eng. 2006;34(11):1655–65.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Balachandran K, Sucosky P, Jo H, Yoganathan AP. Elevated cyclic stretch alters matrix remodeling in aortic valve cusps: implications for degenerative aortic valve disease. Am J Physiol Heart Circ Physiol. 2009;296(3):H756–64.

    Article  CAS  PubMed  Google Scholar 

  52. Sacks MS, Smith DB, Hiester ED. A small angle light scattering device for planar connective tissue microstructural analysis. Ann Biomed Eng. 1997;25(4):678–89.

    Article  CAS  PubMed  Google Scholar 

  53. Amini R, Eckert CE, Koomalsingh K, McGarvey J, Minakawa M, Gorman JH, et al. On the in vivo deformation of the mitral valve anterior leaflet: effects of annular geometry and referential configuration. Ann Biomed Eng. 2012;40(7):1455–67.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Carruthers CA, Alfieri CM, Joyce EM, Watkins SC, Yutzey KE, Sacks MS. Gene expression and collagen Fiber micromechanical interactions of the semilunar heart valve interstitial cell. Cell Mol Bioeng. 2012;5(3):254–65.

    Article  CAS  PubMed  Google Scholar 

  55. Lee CH, Rabbah JP, Yoganathan AP, Gorman RC, Gorman JH 3rd, Sacks MS. On the effects of leaflet microstructure and constitutive model on the closing behavior of the mitral valve. Biomech Model Mechanobiol. 2015;14(6):1281–302.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Khalighi AH, Drach A, Bloodworth CH, Pierce EL, Yoganathan AP, Gorman RC, et al. Mitral valve chordae tendineae: topological and geometrical characterization. Ann Biomed Eng. 2017;45(2):378–93.

    Article  PubMed  Google Scholar 

  57. Khalighi AH, Drach A, Gorman RC, Gorman JH 3rd, Sacks MS. Multi-resolution geometric modeling of the mitral heart valve leaflets. Biomech Model Mechanobiol. 2018;17(2):351–66.

    Article  PubMed  Google Scholar 

  58. Drach A, Khalighi AH, Sacks MS. A comprehensive pipeline for multi-resolution modeling of the mitral valve: validation, computational efficiency, and predictive capability. Int J Numer Methods Biomed Eng. 2018;34(2)

    Article  Google Scholar 

  59. Sacks MS, Khalighi A, Rego B, Ayoub S, Drach A. On the need for multi-scale geometric modelling of the mitral heart valve. Healthc Technol Lett. 2017;4(5):150.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Institutes of Health (NIH) Grants R01HL119297. CHL was in part supported by start-up funds from the School of Aerospace and Mechanical Engineering (AME) at the University of Oklahoma, and the American Heart Association Scientist Development Grant Award (16SDG27760143).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael S. Sacks .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Khang, A., Buchanan, R.M., Ayoub, S., Rego, B.V., Lee, CH., Sacks, M.S. (2018). Biological Mechanics of the Heart Valve Interstitial Cell. In: Sacks, M., Liao, J. (eds) Advances in Heart Valve Biomechanics. Springer, Cham. https://doi.org/10.1007/978-3-030-01993-8_1

Download citation

Publish with us

Policies and ethics