Preconditioning of primary human endothelial cells with inflammatory mediators alters the “set point” of the cell

SPECIFIC AIMSEndothelial cells are highly sensitive to changes in the extracellular milieu. Sepsis (defined as the systemic inflammatory response to infection) results in activation of inflammatory and coagulation pathways. We hypothesized that sepsis-associated mediators may alter the signal transduction capacity (termed “set point”) of endothelial cells. The aim of this study was to elucidate the effect of preconditioning on thrombin-mediated gene expression in human umbilical vein endothelial cells (HUVEC)PRINCIPAL FINDINGS1. Net signal input is crucial in modulating subsequent thrombin signaling in endothelial cellsTo determine the effect of different sepsis-like preconditioning regimes on thrombin-mediated gene expression, HUVEC were pretreated for 16 h in the presence or absence of high glucose, tumor necrosis factor α (TNF-α), and/or lipopolysaccharide (LPS), then treated with or without 1.5 U/mL thrombin for 4 h. Alternatively, HUVEC were grown under hypoxic or hyperthermic conditions prior to thr...