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- Title
Activated protein C inhibits tissue plasminogen activator–induced brain hemorrhage.
- Authors
Cheng, Tong; Petraglia, Anthony L.; Li, Zhang; Thiyagarajan, Meenakshisundaram; Zhong, Zhihui; Wu, Zhenhua; Liu, Dong; Maggirwar, Sanjay B.; Deane, Rashid; Fernández, José A.; LaRue, Barbra; Griffin, John H.; Chopp, Michael; Zlokovic, Berislav V.
- Abstract
Brain hemorrhage is a serious complication of tissue plasminogen activator (tPA) therapy for ischemic stroke. Here we report that activated protein C (APC), a plasma serine protease with systemic anticoagulant, anti-inflammatory and antiapoptotic activities, and direct vasculoprotective and neuroprotective activities, blocks tPA-mediated brain hemorrhage after transient brain ischemia and embolic stroke in rodents. We show that APC inhibits a pro-hemorrhagic tPA-induced, NF-κB–dependent matrix metalloproteinase-9 pathway in ischemic brain endothelium in vivo and in vitro by acting through protease-activated receptor 1. The present findings suggest that APC may improve thrombolytic therapy for stroke, in part, by reducing tPA-mediated hemorrhage.
- Subjects
CEREBRAL hemorrhage; TISSUE plasminogen activator; TRANSIENT ischemic attack; BLOOD coagulation factors; THROMBOLYTIC therapy; BLOOD-brain barrier
- Publication
Nature Medicine, 2006, Vol 12, Issue 11, p1278
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm1498