HEMODYNAMIC FORCES ARE COMPLEX REGULATORS OF ENDOTHELIAL GENE-EXPRESSION

Vascular endothelial cells, by virtue of their unique anatomical position, are constantly exposed to the fluid mechanical forces generated by flowing blood, In vitro studies with model flow systems have demonstrated that wall shear stresses can modulate various aspects of endothelial structure and function, Certain of these effects appear to result from the regulation of expression of endothelial genes at the transcriptional level, Recent molecular biological studies have defined a ''shear stress response element'' (SSRE) in the promoter of the human platelet derived growth factor (PDGF)-B chain gene that interacts with DNA binding proteins in the nuclei of shear-stressed endothelial cells to up-regulate transcriptional activity. Insertion of this element into reporter genes also renders them shear-inducible, Further characterization of this and other positive (and negative) shear-responsive genetic: regulatory elements, as well as their transactivating factors, should enhance our understanding of vascular endothelium as an integrator of humoral and biomechanical stimuli in health and disease.