The protein C pathway plays a key role in the regulation of coagulation and inflammation. Protein C is a zymogen that is activated to its enzymatic form on the vascular endothelium by thrombin complexed to an ubiquitous endothelial cell membrane receptor, thrombomodulin.
Activated protein C (APC) inactivates factors Va and VIIIa, thereby dampening thrombin formation and clotting.
Furthermore APC has direct and indirect anti-inflammatory actions. It prevents leucocyte rolling, tissue factor exposure and tumor necrosis factor production by monocytes, thrombin-mediated inflammatory actions and apoptosis of endothelial cells [Van de Wouwer et al., 2004]
. The latter function is mediated by endothelial protein C/APC receptor (EPCR), another transmembrane protein, which also participates in protein C activation [Van de Wouwer et al., 2004]
Protein C and APC can both bind to EPCR. When APC is bound to EPCR, it changes its substrate specificity and looses its ability to inactivate factors V and VIII, and it acquires the capacity for protease activated receptor- 1 (PAR-1) cleavage, through which, in cooperation with EPCR, it elicits anti-apoptotic effects in the endothelial cells [Van de Wouwer et al., 2004]
. APC is aided in its anticoagulant functions by protein S.