Biomechanics and Modeling in Mechanobiology

, Volume 13, Issue 6, pp 1209–1225 | Cite as

Bicuspid aortic valve hemodynamics induces abnormal medial remodeling in the convexity of porcine ascending aortas

  • Samantha K. Atkins
  • Kai Cao
  • Nalini M. Rajamannan
  • Philippe Sucosky
Original Paper

Abstract

The type-I bicuspid aortic valve (BAV), which differs from the normal tricuspid aortic valve (TAV) most commonly by left-right coronary cusp fusion, is frequently associated with secondary aortopathies. While BAV aortic dilation has been linked to a genetic predisposition, hemodynamics has emerged as a potential alternate etiology. However, the link between BAV hemodynamics and aortic medial degeneration has not been established. The objective of this study was to compare the regional wall shear stresses (WSS) in a TAV and BAV ascending aorta (AA) and to isolate ex vivo their respective impact on aortic wall remodeling. The WSS environments generated in the convex region of a TAV and BAV AA were predicted through fluid–structure interaction (FSI) simulations in an aorta model subjected to both valvular flows. Remodeling of porcine aortic tissue exposed to TAV and BAV AA WSS for 48 h in a cone-and-plate bioreactor was investigated via immunostaining, immunoblotting and zymography. FSI simulations revealed the existence of larger and more unidirectional WSS in the BAV than in the TAV AA convexity. Exposure of normal aortic tissue to BAV AA WSS resulted in increased MMP-2 and MMP-9 expressions and MMP-2 activity but similar fibrillin-1 content and microfibril organization relative to the TAV AA WSS treatment. This study confirms the sensitivity of aortic tissue to WSS abnormalities and demonstrates the susceptibility of BAV hemodynamic stresses to focally mediate aortic medial degradation. The results provide compelling support to the important role of hemodynamics in BAV secondary aortopathy.

Keywords

Bicuspid aortic valve Aortic disease  Fluid–structure interaction modeling Fluid shear stress  Matrix metalloproteinases 

Notes

Acknowledgments

This research was supported in part by a National Science Foundation faculty early CAREER Grant CMMI-1148558, an American Heart Association scientist development Grant 11SDG7600103 and Faculty Seed Funds from the College of Engineering at the University of Notre Dame. The authors would like to thank Andrew McNally and Ling Sun for their technical assistance.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Samantha K. Atkins
    • 1
  • Kai Cao
    • 1
  • Nalini M. Rajamannan
    • 2
  • Philippe Sucosky
    • 3
  1. 1.Department of Aerospace and Mechanical EngineeringUniversity of Notre DameNotre DameUSA
  2. 2.Molecular Biology and BiochemistryMayo Clinic School of MedicineRochesterUSA
  3. 3.Department of Aerospace and Mechanical Engineering, Eck Institute for Global HealthUniversity of Notre DameNotre DameUSA

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