Activated protein C: a promising drug with multiple effects?
The anti-coagulant activated protein C (APC) can exert direct effects on cells, including cytoprotective functions involving apoptosis and inflammation mechanisms. These cytoprotective properties of APC require the presence of protease-activated receptor-1 (PAR-1) and endothelial protein C receptor (EPCR) resulting in inhibition of inflammatory gene expression and down-regulation of p53 and Bax. Several in vitro and animal studies have documented such cytoprotective properties of APC. The first evidence for a cytoprotective role of APC in a clinical setting came from the PROWESS trial in which APC administration reduced mortality rates in severe sepsis patients. However, although APC certainly has the potential to be used in a broader range of clinical settings it is thwarted by the associated risk of bleeding. Further research within this area towards improved therapeutics of specific APC mutants has taken place.
Loubele
S T B G
ST
Maastricht University Medical Center+, Departments of Internal Medicine and Biochemistry, Laboratory for Clinical Thrombosis and Haemostasis, P.O. Box 616, Uns 50: Box 8, 6200 MD Maastricht, The Netherlands. sarah.loubele@bioch.unimaas.nl
Spronk
H M H
HM
Ten Cate
H
H
D000818:Animals; D000925:Anticoagulants / Q000378:metabolism / Q000494:pharmacology; D002477:Cells / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection; D004789:Enzyme Activation; D006801:Humans; D011486:Protein C / Q000378:metabolism* / Q000494:pharmacology*; D015398:Signal Transduction
D000925:Anticoagulants; D011486:Protein C