Role of murine integrin α2β1 in thrombus stabilization and embolization: Contribution of thromboxane A2

Marijke J. E. Kuijpers; Miroslava Pozgajova; Judith M. E. M. Cosemans; Imke C. A. Munnix; Beate Eckes; Bernhard Nieswandt; Johan W. M. Heemskerk

doi:10.1160/TH07-02-0089

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(05): 1072-1080
DOI: 10.1160/TH07-02-0089

Platelets and Blood Cells

Schattauer GmbH

Role of murine integrin α2β1 in thrombus stabilization and embolization: Contribution of thromboxane A₂

Marijke J. E. Kuijpers

¹Departments of Biochemistry, University of Maastricht, Maastricht, The Netherlands

,

Miroslava Pozgajova

³Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany

,

Judith M. E. M. Cosemans

¹Departments of Biochemistry, University of Maastricht, Maastricht, The Netherlands

²Departments of Human Biology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands

,

Imke C. A. Munnix

¹Departments of Biochemistry, University of Maastricht, Maastricht, The Netherlands

,

Beate Eckes

⁴Department of Dermatology, University of Cologne, Cologne, Germany

,

Bernhard Nieswandt

³Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany

,

Johan W. M. Heemskerk

¹Departments of Biochemistry, University of Maastricht, Maastricht, The Netherlands

²Departments of Human Biology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands

› Author Affiliations

Abstract

Summary

Platelets stably interact with collagen via glycoprotein (GP)VI and α2β1 integrin. With α2-null mice, we investigated the role of α2β1 in thrombus formation and stability in vivo and in vitro. Using a FeCl3-induced thrombosis model, in arteries from α2-null mice smaller thrombi were formed with more embolization compared to vessels from wild-type mice. Aspirin treatment of wild-type mice causes similar effects, while the thromboxane A₂ analogue U46619 was borderline effective in suppressing the embolisation in α2-null mice. In vitro, perfusion of α2-null blood over collagen resulted in formation of thrombi that were smaller and looser in appearance, regardless of the presence or absence of coagulation. Aspirin treatment or blockage of thromboxane receptors provoked embolus formation in wildtype blood, while U46619 normalized thrombus formation in blood from α2-null mice. We conclude that integrin α2β1 plays a role in stabilizing murine thrombi, likely by enhancing GPVI activation and thromboxane A₂ release. The increased embolization in α2-null mice may argue against the use of α2β1 integrin inhibitors for antithrombotic therapy.

Keywords

Collagen receptors - integrins - mice - platelets - thrombus

Full Text

References

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