Regulation of Genetic Expression in Shear Stress-stimulated Endothelial Cells

There is increasing evidence that endothelial cells respond to the initiation of mechanical stress by the generation of certain second messengers and the activation of specific metabolic pathways. These rapid alterations in cellular function are accompanied by alterations in protein synthesis that are detectable several hours after initiation of the mechanical stress. The molecular mechanisms by which changes in the cytosol are converted to altered genetic expression in the nucleus are not known. Because agonist-induced modulations in the rate of synthesis of tPA and ET have been associated with the Fos and Jun protein families, it seems reasonable to propose that genetic expression in shear stress- or mechanical strain-stimulated endothelial cells is also regulated by selective induction of fos and jun gene products. Testing of this hypothesis is actively under way in our laboratory.