PAR1 biased signaling is required for activated protein C in vivo benefits in sepsis and stroke

Authors: Ranjeet Sinha, Yaoming Wang, Zhen Zhao, Xiao Xu, Laurent Burnier, Naveen Gupta, José A. Fernández, Greg Martin, S.V. Kupriyanov, Laurent O. Mosnier, Berislav V. Zloković, John H. Griffin - Blood 2018 cited by 104

< .01) but had no benefit for QQ46-PAR1 mice. In transient distal middle cerebral artery occlusion stroke studies, exogenous APC significantly reduced infarct size, edema, and neuronal apoptosis for Wt mice and QQ41-PAR1 mice but had no detectable benefits for mice carrying QQ46-PAR1. In functional studies of forelimb-asymmetry and foot-fault tests at 24 hours after stroke induction, signaling-selective APC was beneficial for Wt and QQ41-PAR1 mice but not QQ46-PAR1 mice. These results support the concept that APC-induced, PAR1-dependent biased signaling following R46 cleavage is central to the in vivo benefits of APC.