The effect of physiological stretch and the valvular endothelium on mitral valve proteomes

Heart valves reside in a dynamic mechanical environment experiencing a multitude of forces. These forces have been shown to play a key role in valvular pathophysiology. However, knowledge of proteins involved in valvular mechanobiology is limited to only a few proteins of interest, namely, alpha-smooth muscle actin, transforming growth factor beta, etc. Valvular endothelium mediates valvular homeostasis and controls valvular interstitial cell phenotype transformation. But, how endothelium mediates valvular response to dynamic forces is also unknown. In this study, proteomic analysis of mitral valve anterior leaflets under 10% cyclic radial strain was performed. Endothelium from these samples was removed to test how endothelium mediates mitral valve response to stretch. Results show that stretch downregulated cytoskeletal proteins and proteins involved in energy metabolism such as glycolysis and oxireductase activity. Endothelium removal resulted in downregulation of extracellular matrix and cell-matrix adhesion proteins. Removal of endothelium also resulted in upregulation of translation-related and chaperone proteins. Overall, this high throughput study provides insights into new protein groups that may be involved in mitral valve response to mechanical stretch and loss of endothelium.