Differential neuroprotection and risk for bleeding from activated protein C with varying degrees of anticoagulant activity.

ABSTRACT:

Background and purpose

Activated protein C (APC), a protease with anticoagulant and cytoprotective activities, protects neurons and endothelium from ischemic injury. Drotrecogin-alfa activated, a hyperanticoagulant form of human recombinant APC, is currently being studied in patients with ischemic stroke. How changes in APC anticoagulant activity influence APC's neuroprotection and risk for bleeding is not clear.

Methods

We used neuronal and brain endothelial cell injury models and middle cerebral artery occlusion in mice to compare efficacy and safety of drotrecogin-alfa activated and human 3K3A-APC, an APC nonanticoagulant mutant.

Results

Drotrecogin-alfa activated and 3K3A-APC exhibited 148% and 10% of plasma-derived APC's anticoagulant activity and differ in the c

SUBMITTER: Wang Y 

PROVIDER: S-EPMC2691176 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature