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

Author:

Massberg Steffen12,Brand Korbinian3,Grüner Sabine1,Page Sharon3,Müller Elke1,Müller Iris1,Bergmeier Wolfgang4,Richter Thomas2,Lorenz Michael1,Konrad Ildiko1,Nieswandt Bernhard4,Gawaz Meinrad12

Affiliation:

1. Deutsches Herzzentrum und 1. Medizinische Klinik, Technische Universität München, D-80636 München, Germany

2. Institut für Pathologie, Klinikum rechts der Isar, Technische Universität München, D-80567 München, Germany

3. Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, D-80567 München, Germany

4. Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, D-97078 Würzburg, Germany

Abstract

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)Ibα 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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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