Background: Vascular endothelial cell activation and dysfunction is observed in patients with severe heart failure and may contribute to systemic manifestations of this syndrome. It remains unknown whether inflammatory activation of these cells occurs in these patients because of increased circulating pro-inflammatory mediators. Aim: to determine whether the serum from patients with heart failure possesses a net pro-inflammatory bioactivity to active pro-inflammatory pathways in cultured endothelial cells. Methods: Serum was obtained from stable end-stage heart failure patients undergoing elective cardiac transplantation (Tx) and severely decompensated heart failure patients requiring emergency LVAD implantation. Net pro-inflammatory bioactivity of serum was investigated by monitoring IB degradation and E-selectin expression in cultured human pulmonary artery endothelial cells (HPAEC) following incubation with serum samples. Serum cytokines concentrations were measured by ELISA and neutralizing antibodies used to determine the role of specific factors in the observed bioactivity. Result: Serum from both patient groups induced HPAEC IB degradation. Low basal HPAEC E-selectin expression significantly increased following treatment with Tx but not LVAD serum. Serum TNF and IL-10 concentrations were higher in LVAD than Tx patients and sTNFR expression was high in both groups. Neither TNFa nor IL-10 blocking experiments altered either bioassay result. Conclusion. Activation of a specific profile of pro and anti-inflammatory mediators is associated with Heart failure resulting in HPAEC NFB activation. However E-selectin expression is further regulated by unidentified factors. TNF is upregulated but appears to play no part in NFB activation in these patients. These findings could have important therapeutic implications.