Title:Thrombomodulin – A New Target for Treating Stroke at the Crossroad of Coagulation and Inflammation
VOLUME: 21 ISSUE: 18
Author(s):J. Wenzel, J.C. Assmann and M. Schwaninger
Affiliation:Institute of Experimental and Clinical Pharmacology and Toxicology, University of Luebeck, Ratzeburger Allee 160, 23562 Luebeck, Germany.
Keywords:Cerebral blood flow, cerebral ischemia, coagulation, endothelial cells, endothelial NO synthase, inflammation, protein
C system, soluble thrombomodulin, TAFI, vascular permeability.
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.
