This research project will investigate the influence of mechanical stress on the growth programs of vascular endothelial cell in vitro, including signal transduction mechanisms. Endothelial cell, as well as other cell types for comparison, will be studied in different mechanical stress environments, and alterations in endothelial cell growth programs will be determined through measurements of cell proliferation and the expression of growth-related genes. A common set of membrane signaling mechanisms may be involved in both cytoskeletal rearrangement and growth program changes induced by endothelial cells in mechanical stresses, and regional alterations in intracellular calcium ion concentrations to cytoskeletal rearrangements will be assessed. In vivo endothelial cells are in a non-growth promoting mode, while in vitro basally release growth promoting substances. This difference is believed to be due to the artificial, non-physiologic nature of the static culture environment, which is devoid of mechanical stress. The results should allow cell culture environments to be engineered so as to make the cell culture more like a natural environment. This procedure will aid in using culture experiments to understand the processes involved in the maintenance, repair, and growth of vascular components.
