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

Vascular endothelial cells are exposed to a complex humoral and hemody namic environment. Investigations over the last two decades have demon strated 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 currentl y is not a known unifying mechanism linking mechanical agonists to cha nges in gene expression, various second messengers, transcription fact ors, mechanically sensitive promoter elements, and cytoskeletal archit ecture have been proposed as mediators in the signal transduction path way. Knowledge of the mechanisms by which hemodynamic forces modulate endothelial cell gene expression will lead to novel gene therapy appli cations and allow more effective management of cardiovascular diseases .