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.
Griffin
John H
JH
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 N. Torrey Pines Road, MEM-180, La Jolla, CA 92037, USA.
Zlokovic
Berislav
B
Fernández
José A
JA
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