on February 1, 2007
Published online before print February 1, 2007, doi: 10.1161/01.ATV.0000259359.52265.62
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Submitted on November 30, 2006
Accepted on January 23, 2007
Platelet Adhesion Receptors and Their Ligands in Mouse Models of Thrombosis
Cécile V. Denis and Denisa D. Wagner *
From INSERM U770 (C.V.D.), Univ Paris-Sud, Le Kremlin-Bicêtre, France, and the CBR Institute for Biomedical Research and Department of Pathology (D.D.W.), Harvard Medical School, Boston Mass.
* To whom correspondence should be addressed. E-mail: wagner{at}cbr.med.harvard.edu.
Abstract--Platelet adhesion and aggregation at sites of vascular injury are 2 key events in hemostasis and thrombosis. Because of exciting advances in genetic engineering, the mouse has become an important and frequently used model to unravel the molecular mechanisms underlying the multistep process leading to the formation of a stable platelet plug. In gene-targeted mice, the crucial importance of platelet adhesion receptors such as glycoprotein Ib
or the IIb
3 integrin has been confirmed and further clarified. Their absence leads to highly impaired thrombus formation, independent of the model used to induce vascular injury. In contrast, the relative contribution of other receptors, such as glycoprotein VI, or of various platelet ligands may be regulated by the severity of injury, the type of vessel injured, and the signaling pathways that are generated. Murine models have also helped improve understanding of the second wave of events that leads to stabilization of the platelet aggregate. Despite the current limitations due to lack of standardization and the virtual absence of thrombosis models in diseased vessels, there is no doubt that the mouse will play a key role in the discovery and characterization of the next generation of antithrombotic agents. This review focuses on key findings about the molecular mechanisms supporting hemostasis and thrombosis that have been obtained with genetically engineered mouse models deficient in various platelet adhesion receptors and ligands. Combination of these models with sophisticated methods allowing direct visualization of platelet-vessel wall interactions after injury greatly contributed to recent advances in the field.
Key words: platelets • animal models • thrombosis • adhesion • bleeding
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