Vorapaxar, but not parmodulin 2, blocks APC-mediated cytoprotection in endothelial cells. (A) Mock-transfected and PAR1 siRNA–transfected (siPAR1) HUVECs were incubated in the presence of buffer (N/A) or APC before exposure to vehicle or TNF-α. Incubation with APC inhibits apoptosis induced by TNF-α in mock-transfected HUVECs, but not cells in which PAR1 has been knocked down. (B) Endothelial cells were incubated in the presence of vehicle (white), 10 μM parmodulin 2 (black), or 0.3 μM vorapaxar (gray) for 30 minutes. Samples were then exposed to either buffer or APC for 4 hours. Indicated samples were subsequently stimulated with TNF-α and analyzed for apoptosis. Data are presented as means ± SEM (n = 5). *P < .05, **P < .01.