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Bicuspid Aortic Valve Hemodynamics Contribute to Acute Remodeling in Porcine Ascending Aortas
Samantha Ratley, Kai Cao, Philippe Sucosky.
University of Notre Dame, South Bend, IN, USA.

OBJECTIVE: The type-I bicuspid aortic valve (BAV), which differs from the normal tricuspid aortic valve (TAV) 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 the TAV and BAV ascending aorta (AA) and to isolate ex vivo their respective impact on aortic wall remodeling.
METHODS: 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 hours in a cone-and-plate bioreactor was investigated via immunostaining, immunoblotting, zymography, and gene analysis.
RESULTS: 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 protein expressions and MMP-2 activity but similar fibrillin-1 content and microfibril organization relative to the TAV AA WSS treatment. Gene analysis on the expression levels of the ratio of matrix metalloproteinases (MMPs) to their inhibitors, TIMPs, showed that the BAV AA convexity has a higher ratio of MMP-9/TIMP-1.
CONCLUSIONS: 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 increased ratio of MMP-9 to TIMP-1 indicates accelerated remodeling events at 48 hours as compared to TAV AA WSS conditioned tissue and fresh tissue. The results provide compelling support to the dominant role of hemodynamics in BAV secondary aortopathy.

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