Endothelial gene regulation by laminar shear stress.

Endothelial cells, because of their unique localization, are constantly exposed to fluid mechanical forces derived by the flowing blood. These forces, and more specifically shear stresses; affect endothelial structure and function, both in vivo and in vitro, and are implicated as contributing factors in the development of cardiovascular diseases. We have demonstrated earlier that the shear stress selectively induces the transcription of several endothelial genes, and have defined a shear stress response element (SSRE) in the promoter of platelet-derived-growth-factor B (PDGF-B), that is shared by additional endothelial shear stress responsive genes. Here we further characterize this SSRE and the nuclear factors that bind to it, and imply the possible role of the endothelium cytoskeleton in transducing shear stress, leading to the expression of PDGF-B/SSRE constructs in transfected endothelial cells exposed to shear stress. We also present, yet a new shear stress response element in the Platelet Derived Growth Factor A promoter, that contains a binding site to the transcription factors egr1/sp1. These results further demonstrate the complexity of gene regulation by hemodynamic forces, and support the important part that these forces have in the physiology and pathophysiology of the vessel wall.