(721d) Differential Endothelial Cell Response to Simultaneous Shear and Cytokine Stimulation

Endothelial cells are continuously exposed to in vivo hemodynamic forces imparted by blood flow. At the interface between the vascular wall and the bloodstream, these cells are responsible for modulating numerous critical processes including angiogenesis, clotting and thrombosis, control of blood pressure, and inflammation. Their response to fluid shear stress and various chemical agonists is critical to their role in physiology or disease pathology. Despite this potential, the mechanisms of endothelial behavior are still largely not understood. While it is well known that endothelial behavior can be modulated individually by cytokine activation or fluid shear imparted by blood flow, the combined effects of shear and cytokine activation have not yet been fully elucidated with some literature reporting contradicting theories. Additionally, few have observed prolonged endothelial cell response during which phenotype drastically changes. Here, we explore the potential effects of shear-based interleukin-1beta (IL-1beta)-induced changes in modulating endothelial phenotype via upregulation of adhesion molecules. We find that exposure of endothelial cells to physiological shear stress in the presence of activating IL-1beta at different time points results in differential expression of adhesion molecules, e.g. E-selectin, unlike shear or cytokine (static) exposure alone. Overall, the presented data suggests endothelial cells have an increasingly complex response when exposed to multiple stimuli, as is the case in many physiological and pathological conditions. Elucidating endothelial responses relative to quiescent states could have potential use in diagnostic and therapeutic applications.