Activated protein C in sepsis and beyond: update 2006.

Activated protein C (APC), a plasma serine protease, is best known for its ability to inhibit blood clot formation. APC acts as an anticoagulant by degrading coagulation cofactors Va and VIIIa, thereby attenuating the coagulation cascade. Over the past 15 years, impressive research advances have provided novel insights into the diverse biological activities of this molecule. APC is now viewed not only as an anticoagulant but also as a signaling molecule that provides a pivotal link between the pathways of coagulation, inflammation, apoptosis, and vascular permeability. The protective effect of APC supplementation in patients with severe sepsis likely reflects the ability of APC to modulate multiple pathways implicated in sepsis pathophysiology. This review attempts to summarize key studies that support the therapeutic potential of APC in conditions beyond sepsis such as stroke, ischemia-reperfusion injury, lung injury, asthma, pancreatitis, wound healing, and angiogenesis. A comprehensive PUBMED literature review up to May 2006 was conducted.