The Journal of Experimental Medicine
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Published online 30 September 2002 doi:10.1084/jem.20012044
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© Rockefeller University Press, 0022-1007/2002/10/887/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 7, October 7, 2002 887-896

A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion Formation

Steffen Massberg1,4, Korbinian Brand2, Sabine Grüner1, Sharon Page2, Elke Müller1, Iris Müller1, Wolfgang Bergmeier3, Thomas Richter4, Michael Lorenz1, Ildiko Konrad1, Bernhard Nieswandt3 and Meinrad Gawaz1,4

1 Deutsches Herzzentrum und 1. Medizinische Klinik, Technische Universität München, D-80636 München, Germany
2 Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, D-80567 München, Germany
3 Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, D-97078 Würzburg, Germany
4 Institut für Pathologie, Klinikum rechts der Isar, Technische Universität München, D-80567 München, Germany

Address correspondence to Steffen Massberg and Meinrad Gawaz, Deutsches Herzzentrum und 1. Medizinische Klinik, Technische Universität München, Lazarettstrasse 36, D-80636 München, Germany. Phone: 49-89-1218-4012; Fax: 49-89-1218-4003; E-mail: massberg{at}dhm.mhn.de or gawaz{at}dhm.mhn.de

The contribution of platelets to the process of atherosclerosis remains unclear. Here, we show in vivo that platelets adhere to the vascular endothelium of the carotid artery in ApoE-/- mice before the development of manifest atherosclerotic lesions. Platelet–endothelial cell interaction involved both platelet glycoprotein (GP)Ib{alpha} and GPIIb-IIIa. Platelet adhesion to the endothelium coincides with inflammatory gene expression and preceded atherosclerotic plaque invasion by leukocytes. Prolonged blockade of platelet adhesion in ApoE-/- mice profoundly reduced leukocyte accumulation in the arterial intima and attenuated atherosclerotic lesion formation in the carotid artery bifurcation, the aortic sinus, and the coronary arteries. These findings establish the platelet as a major player in initiation of the atherogenetic process.

Key Words: platelets • endothelium • atherosclerosis • integrin • glycoprotein Ib


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