The Effects of Mechanical Loading on the Local Myofibrogenic Differentiation of Aortic Valve Interstitial Cells

• Main Author: Watt, Derek Randall
• Other Authors: Simmons, Craig Alexander
• Format: Others
• Language: en_ca
• Published: 2008
• Subjects: Mechanobiology; Tissue Engineering; Myofibroblasts; α-Smooth Muscle Actin; Cofilin; Aortic Valve Disease; 0541
• Online Access: http://hdl.handle.net/1807/10442

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.