Fluid shear stress and the vascular endothelium: For better and for worse

As blood flows, the vascular wall is constantly subjected to physical forces, which regulate important physiological blood vessel responses, as well as being implicated in the development of arterial wall pathologies. Changes in blood flow, thus generating altered hemodynamic forces are responsible for acute vessel tone regulation, the development of blood vessel structure during embryogenesis and early growth, as well as chronic remodeling and generation of adult blood vessels. The complex interaction of biomechanical forces, and more specifically shear stress, derived by the flow of blood and the vascular endothelium raise many yet to be answered questions:(1) How are mechanical forces transduced by endothelial cells into a biological response, and is there a "shear stress receptor"?(2) Are "mechanical receptors" and the final signaling pathways they evoke similar to other stimulus-response transduction systems?(3) How do vascular endothelial cells differ in their response to physiological or pathological shear stresses?(4) Can shear stress receptors or shear stress responsive genes serve as novel targets for the design of diagnostic and therapeutic modalities for cardiovascular pathologies? The current review attempts to bring together recent findings on the in vivo and in vitro responses of the vascular endothelium to shear stress and to address some of the questions raised above.