(490a) The Effects of Transforming Growth Factor ß1 Stimulation on Endothelial Cell Physiology Are Influenced by Shear Stress

Atherosclerotic plaques preferentially occur at bifurcation regions exhibiting fluid turbulence and low shear stress while straight sections of artery with less complex hemodynamics and relatively high shear stress are protected. In an effort to examine the relationship between shear stress and the effects of cytokine exposure on human umbilical vein endothelial cells (HUVEC), cells were exposed to continuous pulsatile shear stress for 20 hours prior to a 4-hour Transforming Growth Factor Beta 1 (TGF-ß1) incubation. The expression of several genes was followed at the protein and/or mRNA levels to observe the interaction of different levels of shear stress and TGF-ß1. Results showed that expression of TGF-ß Receptor II, Thrombospondin-1 and ß1 integrin were each altered under the different levels of shear stress. This alteration appeared to coincide with increased activation of Extracellular Regulated Kinase 1/2 (ERK). These results imply a relationship between shear stress, the level of ERK activation, and the sensitivity of HUVEC to exogenously added TGF-ß1. The finding that a physiologically ?low? pulsatile shear stress allowed enhanced TGF-ß1 sensitivity as compared to a physiologically ?normal? level without a significant increase in TGF-ß RII levels suggests an alternate path by which TGF-ß1 can play a role in endothelial dysfunction and atherogenesis.