ABSTRACT
Fluid shear stress is one of the most important hemodynamic forces recognized and transduced by endothelial cells, as it modulates vessel structure and function. Shear stress is also important in the pathogenesis of atherosclerosis because atherosclerotic plaques occur preferentially in areas which experience low shear stress and flow reversal. Changes in shear stress cause rapid secretion of vasoactive mediators, including nitric oxide, prostacyclin, and endothelin. Changes in shear stress also cause long term alterations in vessel structure and3 function by regulating gene and protein
expression. For example, shear stress stimulates expression of platelet-derived growth factor (PDGF) A-and B-chains, tissue plasminogen activator, endothelial nitric oxide synthase and superoxide dismutase. An important question concerns the mechanisms by which shear stress transduces signals that modify endothelial cell function. Experimental evidence indicates that the cellular response to shear stress is similar to the response to classical growth factors (e.g. epidermal growth factor) which involves activation of a complex array of phosphorylation cascades. This concept has been strongly supported by study of the mitogen-activated protein kinase (MAPK) family which plays an integral role in growth factor-mediated signaling and in the endothelial cell response to fluid shear stress. In this chapter, we review mechanisms by which MAPKs are regulated by shear stress and discuss techniques whereby responsiveness to shear stress are easily studied.
