Shear and signal transduction in the endothelial cell

Abstract

Blood vessels are permanently subjected to mechanical forces in the form of stretch and shear stress. Any alterations in the hemodynamic environment invariably produce transformations in the vessel wall that will aim to accommodate the new conditions and to ultimately restore basal levels of mechanical forces. Many receptors, present on the surface of endothelial cells, allow vessels to detect subtle changes in shear stress. Inside the cells, cytoskeletal proteins transmit and modulate the tension between integrins, focal adhesion sites, and the extracellular matrix. Besides inducing structural modifications, mechanical forces lead to changes in the ionic composition of cells, mediated by ion channels, stimulate various membrane receptors, and induce complex biochemical cascades. Many intracellular pathways such as the MAP kinase cascade are activated by shear stress and initiate via sequential phosphorylations the activation of transcription factors and subsequent gene expression. Thus, by purely local mechanisms, blood vessels are capable of true autonomic regulation which enables them to adapt to their mechanical environment.