Semin Thromb Hemost 2017; 43(2): 191-199
DOI: 10.1055/s-0036-1585077
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

α2-Antiplasmin: New Insights and Opportunities for Ischemic Stroke

Guy L. Reed
1   Department of Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee
,
Aiilyan K. Houng
1   Department of Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee
,
Satish Singh
1   Department of Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee
,
Dong Wang
1   Department of Medicine, University of Tennessee Health Sciences Center, Memphis, Tennessee
› Author Affiliations
Further Information

Publication History

Publication Date:
29 July 2016 (online)

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Abstract

Thrombotic vascular occlusion is the leading cause of ischemic stroke. High blood levels of α2-antiplasmin (a2AP), an ultrafast, covalent inhibitor of plasmin, have been linked in humans to increased risk of ischemic stroke and failure of tissue plasminogen activator (tPA) therapy. Consistent with these observations, a2AP neutralizes the therapeutic benefit of tPA therapy in experimental stroke. In addition, a2AP has deleterious, dose-related effects on ischemic brain injury in the absence of therapy. Experimental therapeutic inactivation of a2AP markedly reduces microvascular thrombosis, ischemic brain injury, brain swelling, brain hemorrhage, and death after thromboembolic stroke. These data provide new insights into the critical importance of a2AP in the pathogenesis of ischemic brain injury and suggest that transiently inactivating a2AP may have therapeutic value in ischemic stroke.