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

Mir S. Ali, Xinmei Wang, Carla M.R. Lacerda

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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, α-smooth muscle actin, transforming growth factor β, 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. Impact statement: This work is important to the field of heart valve pathophysiology as it provides new insights into molecular markers of mechanically induced valvular degeneration as well as the protective role of the valvular endothelium. These discoveries reported here advance our current knowledge of the valvular endothelium and how its removal essentially takes valve leaflets into an environmental shock. In addition, it shows that static conditions represent a mild pathological state for valve leaflets, while 10% cyclic stretch provides valvular cell quiescence. These findings impact the field by informing disease stages and by providing potential new drug targets to reverse or slow down valvular change before it affects cardiac function.

Original languageEnglish
Pages (from-to)241-251
Number of pages11
JournalExperimental Biology and Medicine
Volume244
Issue number3
DOIs
StatePublished - Mar 1 2019

Keywords

  • Mitral valve
  • cyclic stretch
  • endothelial cells
  • interactome
  • mechanotransduction
  • proteome

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