The normal role of Activated Protein C in maintaining homeostasis and its relevance to critical illness.
Thrombin is a multifunctional protein, with procoagulant, inflammatory and anticoagulant effects. Binding of thrombin to thrombomodulin results in activation of Protein C and initiation of the Activated Protein C anticoagulant pathway, a process that is augmented by the endothelial cell Protein C receptor (EPCR). Activated Protein C has demonstrated antithrombotic, anti-inflammatory, and profibrinolytic properties. Its antithrombotic activity is particularly important in the microcirculation, and Protein C deficiency is associated with microvascular thrombosis. Activated Protein C has also been shown to modulate inflammation. When the level of thrombomodulin or Protein C is reduced in sepsis there is a vicious cycle of coagulation and inflammation, with potentially lethal consequences. In vitro studies and animal models have shown that Activated Protein C blunts the inflammatory and coagulant response to sepsis through a variety of mechanisms.
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Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Howard Hughes Medical Institute, Oklahoma City 73104, USA. Charles-Esmon@omrf.ouhsc.edu
D000818:Animals; D001777:Blood Coagulation / Q000502:physiology; D016638:Critical Illness; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008833:Microcirculation / Q000502:physiology; D011486:Protein C / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism*; D018180:Thrombomodulin / Q000378:metabolism
D011486:Protein C; D018180:Thrombomodulin