Activated protein C: potential therapy for severe sepsis, thrombosis, and stroke.
Activated protein C (APC) reduced all-cause 28-day mortality by 19% in patients with severe sepsis (sepsis associated with acute organ dysfunction) in the Protein C Evaluation in Severe Sepsis (PROWESS) trial, leading to recent approval of recombinant APC for treatment of this condition in adults. This review summarizes current knowledge derived from studies of a variety of animal models in which infused human APC demonstrated beneficial activities. Based on in vivo and also in vitro data, APC manifests antithrombotic, profibrinolytic, anti-inflammatory, and antiapoptotic activities. APC is a normal circulating component of plasma, derived from the protein C zymogen, and is thus a natural endogenous protective homeostatic factor. Because of its multiple activities, APC has a potential role in the treatment of complex and challenging medical disorders, including thrombosis and stroke.
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N. Torrey Pines Road, MEM-180, La Jolla, CA 92037, USA.
John H
JH
Griffin
Berislav
B
Zlokovic
José A
JA
Fernández
D006801:Humans; D011486:Protein C / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy / Q000209:etiology; D020521:Stroke / Q000188:drug therapy; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000188:drug therapy
D011486:Protein C; D013917:Thrombin