Exogenous HMGB1 exacerbates hypoxia-induced endothelial dysfunction and inflammation. WT and Tlr4−/− mice were treated with recombinant human HMGB1 (10 µg/day IP) during 10 d of chronic hypoxia and were assessed for plasma ET-1 (A) and sICAM levels (B) in lung homogenates. WT and Tlr4−/− mice injected with sterile saline served as controls (A, B). Data represent the mean ± SEM of six mice per group. Analysis of variance: *P < 0.05. (C) Effect of TLR4-neutralizing antibody (20 µg/mL) on HMGB1 induced ET-1 release in human pulmonary artery endothelial cells. Data represent the mean ± SEM of three independent experiments. Analysis of variance: *P < 0.05. n.s., Not significant.