SHEAR-STRESS AND CYCLIC STRAIN MODULATION OF GENE-EXPRESSION IN VASCULAR ENDOTHELIAL-CELLS

Vascular endothelial cells are exposed to a complex humoral and hemodynamic environment. Investigations over the last two decades have demonstrated that hemodynamic forces cause alterations in endothelial cell function. More specifically, blood flow-induced wall shear stress and cyclic strain modulate gene expression of various bioactive molecules synthesized and secreted by endothelial cells. Although there currently is not a known unifying mechanism linking mechanical agonists to changes in gene expression, various second messengers, transcription factors, mechanically sensitive promoter elements, and cytoskeletal architecture have been proposed as mediators in the signal transduction pathway. Knowledge of the mechanisms by which hemodynamic forces modulate endothelial cell gene expression will lead to novel gene therapy applications and allow more effective management of cardiovascular diseases.