The anticoagulant and anti-inflammatory roles of the protein C anticoagulant pathway

Recent research has revealed a number of links between inflammation and coa gulation. The protein C anticoagulant pathway appears to be the major pathw ay involved in the cross-talk between inflammation and coagulation. Studies indicate that inflammatory mediators can downregulate key components of th e pathway through transcriptional control, proteolytic inactivation and oxi dant damage. In turn, in vine and in vitro studies have revealed mechanisms by which the components of the pathway map inhibit inflammatory responses. These include inhibition of cytokine responses to endotoxin, inhibition of leukocyte attachment to the activated endothelium and inhibition of thromb in and factor Xa generation in the microcirculation where both enzymes can lead to endothelial cell activation, further potentiating the inflammatory response. The ability of the protein C system to modulate both inflammation and coagulation may explain in part why specific defects in the pathway ap pear to be associated with both arterial and venous thrombosis. (C) 2000 Ac ademic Press.