Effect of LP11 on APC-mediated endothelial barrier function. (A) APC (40 nM) barrier protective effect in the presence of LP11 against barrier permeability induced by thrombin (0.25 nM). Shown is the cell index normalized (NCI) to the time of thrombin addition (n = 4). (B) Quantification of APC barrier protective effects the presence of LP11 shown in panel A was based on the lowest NCI value of each time course, with the APC effect in the absence of LP11 set to 100% and the thrombin alone group as 0%. (C) Transient endothelial barrier disruption shortly after the APC priming of the EA.hy926 cells (n = 4). (D) Quantification of the transient barrier disruption upon APC priming in panel C. (E) Inhibition of the transient barrier disruption by APC priming (40 nM) using PAR1 antagonists, vorapaxar (1 μM) or SCH79797 (1 μM; n = 3). (F) Inhibition of the transient endothelial cell barrier disruption upon APC priming (40 nM) in the presence of LP11 (n = 4). (G) Quantification of the transient barrier disruption upon APC priming in panel F. (H) Overall profile of the changes in the NCI to the time of APC addition to the cells (APC priming).