Abstract
OBJECTIVE - Thrombin containing the mutations Trp215Ala and Glu217Ala (WE) selectively activates protein C and has potent antithrombotic effects in primates. The aim of this study was to delineate the molecular mechanism of direct WE-platelet interactions under static and shear conditions. METHODS AND RESULTS - Purified platelets under static conditions bound and spread on immobilized wild-type but not WE thrombin. In PPACK-anticoagulated blood under shear flow conditions, platelets tethered and rolled on both wild-type and WE thrombin, and these interactions were abrogated by the presence of a glycoprotein Ib (GPIb)-blocking antibody. Platelet deposition on collagen was blocked in the presence of WE, but not wild-type thrombin or prothrombin. WE also abrogated platelet tethering and rolling on immobilized von Willebrand factor in whole blood under shear flow. CONCLUSIONS - These observations demonstrate that the thrombin mutant WE, while not activating platelets, retains the ability to interact with platelets through GPIb, and inhibits GPIb-dependent binding to von Willebrand factor-collagen under shear.
Original language | English (US) |
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Pages (from-to) | 329-334 |
Number of pages | 6 |
Journal | Arteriosclerosis, thrombosis, and vascular biology |
Volume | 28 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2008 |
Keywords
- GPIb
- Platelet
- Thrombin
- Von Willebrand factor
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine