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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/10442

Title: The Effects of Mechanical Loading on the Local Myofibrogenic Differentiation of Aortic Valve Interstitial Cells
Authors: Watt, Derek Randall
Advisor: Simmons, Craig Alexander
Department: Biomedical Engineering
Keywords: Mechanobiology
Tissue Engineering
Myofibroblasts
α-Smooth Muscle Actin
Cofilin
Aortic Valve Disease
Issue Date: 25-Jul-2008
Abstract: Calcific aortic valve sclerosis is characterized by focal lesions in the valve leaflet. These lesions are rich in myofibroblasts that express α-SMA and cause fibrosis. Lesions tend to occur in regions of the leaflet that are subjected to large bending loads, suggesting a mechanobiological basis for myofibrogenic differentiation and valve pathogenesis. In this thesis, a bioreactor was developed to study the effect of physiological loading on myofibrogenic differentiation of valve interstitial cells. Cyclic loading of native porcine aortic valve leaflets ex vivo resulted in increased α-SMA expression, predominantly in the fibrosa and spongiosa (similar to sclerotic leaflets). Cofilin, an actin-binding protein, was also upregulated by loading, suggesting it plays a role in mechanically-induced myofibrogenesis. Similarly, loading of a tissue engineered aortic valve leaflet model resulted in increased α-SMA transcript and protein expression. These data support an integral role for mechanical stimuli in myofibrogenic differentiation and sclerosis in the aortic valve.
URI: http://hdl.handle.net/1807/10442
Appears in Collections:Master
Institute of Biomaterials and Biomedical Engineering - Master theses

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