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Annals of Biomedical Engineering

, Volume 39, Issue 6, pp 1654–1667 | Cite as

The Effects of Combined Cyclic Stretch and Pressure on the Aortic Valve Interstitial Cell Phenotype

  • Patrick Thayer
  • Kartik Balachandran
  • Swetha Rathan
  • Choon Hwai Yap
  • Sivakkumar Arjunon
  • Hanjoong Jo
  • Ajit P. Yoganathan
Article

Abstract

Aortic valve interstitial cells (VIC) can exhibit phenotypic characteristics of fibroblasts, myofibroblasts, and smooth muscle cells. Others have proposed that valve cells become activated and exhibit myofibroblast or fibroblast characteristics during disease initiation and progression; however, the cues that modulate this phenotypic change remain unclear. We hypothesize that the mechanical forces experienced by the valve play a role in regulating the native phenotype of the valve and that altered mechanical forces result in an activated phenotype. Using a novel ex vivo cyclic stretch and pressure bioreactor, we subjected porcine aortic valve (AV) leaflets to combinations of normal and pathological stretch and pressure magnitudes. The myofibroblast markers α-SMA and Vimentin, along with the smooth muscle markers Calponin and Caldesmon, were analyzed using immunohistochemistry and immunoblotting. Tissue structure was analyzed using Movat’s pentachrome staining. We report that pathological stretch and pressure inhibited the contractile and possibly myofibroblast phenotypes as indicated by downregulation of the proteins α-SMA, Vimentin, and Calponin. In particular, Calponin downregulation implies depolymerization of actin filaments and possible conversion to a more synthetic (non-contractile) phenotype. This agreed well with the increase in spongiosa and fibrosa thickness observed under elevated pressure and stretch that are typically indicative of increased matrix synthesis. Our study therefore demonstrates how cyclic stretch and pressure may possibly act together to modulate the AVIC phenotype.

Keywords

Aortic valve Stretch Pressure Phenotype 

Notes

Acknowledgments

National Science Foundation through the Engineering Research Center program at Georgia Tech/Emory Center for the Engineering of Living Tissues under award EEC-9731643. Holifield Farms for providing porcine hearts for the research. Patrick Thayer was supported by the President’s Undergraduate Research Award (PURA).

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Copyright information

© Biomedical Engineering Society 2011

Authors and Affiliations

  • Patrick Thayer
    • 1
  • Kartik Balachandran
    • 1
  • Swetha Rathan
    • 2
  • Choon Hwai Yap
    • 1
  • Sivakkumar Arjunon
    • 1
  • Hanjoong Jo
    • 3
  • Ajit P. Yoganathan
    • 1
  1. 1.W.H. Coulter School of Biomedical EngineeringGeorgia Institute of TechnologyAtlantaUSA
  2. 2.School of Chemical and Biomolecular EngineeringGeorgia Institute of TechnologyAtlantaUSA
  3. 3.Department of CardiologyEmory UniversityAtlantaUSA

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