Humanized mouse model of thrombosis is predictive of the clinical efficacy of antiplatelet agents.

ABSTRACT:

Background

In vivo testing of novel antiplatelet agents requires informative biomarkers. By genetically modifying mouse von Willebrand factor (VWF(R1326H)), we have developed a small animal model that supports human but not mouse platelet-mediated thrombosis. Here, we evaluate the use of this biological platform as a pharmacodynamic biomarker for antithrombotic therapies.

Methods and results

The antithrombotic effects of several αIIbβ3 inhibitors were determined in VWF(R1326H) mutant mice infused with human platelets. Administration of abciximab, eptifibatide, or tirofiban at doses recommended for percutaneous coronary intervention (per 1 kg of body weight) significantly reduced human platelet-mediated thrombus formation in laser-injured arterioles by > 75% (P < 0.001). In c

SUBMITTER: Magallon J 

PROVIDER: S-EPMC3046630 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature