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Current Medicinal Chemistry
ISSN (Print): 0929-8673
ISSN (Online): 1875-533X
Epub Abstract Ahead of Print
DOI: 10.2174/0929867321666131228204839      Price:  $95









Thrombomodulin – a New Target for Treating Stroke at the Crossroad of Coagulation and Inflammation

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Author(s): Jan Wenzel, Julian Christopher Assmann and Markus Schwaninger
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Abstract:
Thrombomodulin (TM) is a membrane protein mainly expressed by endothelial cells. It is part of the anticoagulant protein C system but recently several effects were discovered which occur independently of protein C activation. TM binds thrombin and promotes the cleavage of protein C and the thrombin activatable fibrinolysis inhibitor (TAFI), thereby inhibiting coagulation and fibrinolysis. Additionally, it interferes with inflammation, stabilizes barrier function, and increases blood flow under pathological conditions. Recombinant soluble TM protects against tissue damage and partially restores normal function after ischemia in several organs. Recently, it was shown to reduce the infarct size in stroke models. Compared to other anticoagulant compounds the risk of bleeding seems to be smaller in animals and humans treated with soluble TM. With its multiple actions TM represents a new candidate for stroke treatment. In this review we focus on the effects of TM in coagulation, inflammation, and on its protective roles in the prevention of ischemic brain damage
Affiliation:
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany