Protein C anticoagulant and cytoprotective pathways
- 5 April 2012
- journal article
- review article
- Published by Springer Science and Business Media LLC in International Journal of Hematology
- Vol. 95 (4), 333-345
- https://doi.org/10.1007/s12185-012-1059-0
Abstract
Plasma protein C is a serine protease zymogen that is transformed into the active, trypsin-like protease, activated protein C (APC), which can exert multiple activities. For its anticoagulant action, APC causes inactivation of the procoagulant cofactors, factors Va and VIIIa, by limited proteolysis, and APC’s anticoagulant activity is promoted by protein S, various lipids, high-density lipoprotein, and factor V. Hereditary heterozygous deficiency of protein C or protein S is linked to moderately increased risk for venous thrombosis, while a severe or total deficiency of either protein is linked to neonatal purpura fulminans. In recent years, the beneficial direct effects of APC on cells which are mediated by several specific receptors have become the focus of much attention. APC-induced signaling can promote multiple cytoprotective actions which can minimize injuries in various preclinical animal injury models. Remarkably, pharmacologic therapy using APC demonstrates substantial neuroprotective effects in various murine injury models, including ischemic stroke. This review summarizes the molecules that are central to the protein C pathways, the relationship of pathway deficiencies to venous thrombosis risk, and mechanisms for the beneficial effects of APC.Keywords
This publication has 159 references indexed in Scilit:
- Cytoprotective protein C pathways and implications for stroke and neurological disordersTrends in Neurosciences, 2011
- Factor VIIa interaction with endothelial cells and endothelial cell protein C receptorThrombosis Research, 2010
- Extracellular histones are major mediators of death in sepsisNature Medicine, 2009
- Thrombomodulin Mutations in Atypical Hemolytic–Uremic SyndromeThe New England Journal of Medicine, 2009
- Regulation of vascular permeability by sphingosine 1-phosphateMicrovascular Research, 2009
- Activated protein C ligation of ApoER2 (LRP8) causes Dab1-dependent signaling in U937 cellsProceedings of the National Academy of Sciences of the United States of America, 2009
- Receptors of the protein C activation and activated protein C signaling pathways are colocalized in lipid rafts of endothelial cellsProceedings of the National Academy of Sciences of the United States of America, 2007
- Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotectiveNature Medicine, 2003
- Mutation in blood coagulation factor V associated with resistance to activated protein CNature, 1994
- Comparative Protein Modelling by Satisfaction of Spatial RestraintsJournal of Molecular Biology, 1993