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Semin Thromb Hemost 2004; 30(4): 419-425
DOI: 10.1055/s-2004-833477
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Platelet-Collagen Responses: Molecular Basis and Therapeutic Promise

Mark L. Kahn1
  • 1Assistant Professor, Division of Cardiology and Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Publication History

Publication Date:
08 September 2004 (online)

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Exposure of circulating blood to collagen after vessel injury has been recognized as a primary event in arterial thrombosis for many years but an understanding of the molecular basis of this response has only recently materialized. Platelet collagen interactions are initiated indirectly by interaction of platelet glycoprotein Ib (GPIb) with collagen-bound von Willebrand Factor (vWF). Slowed, rolling platelets firmly adhere following the generation of platelet activating signals in a process initiated by the platelet collagen receptor glycoprotein VI (GPVI). The contribution of the first platelet collagen receptor identified, integrin α2β1, remains controversial. α2β1 is not required for platelet responses to collagen under many experimental conditions but GPVI and other intracellular signals may activate the integrin, which is likely to play a later, secondary role. In vivo studies of arterial thrombosis using genetically modified mice suggest that blockade of platelet-collagen interactions may be a highly effective means of inhibiting arterial thrombosis. Recent studies have generated a more complete model of the molecular basis of platelet-collagen responses and provided both the means and incentive to create novel therapeutic agents aimed at blocking this process to treat human atherothrombotic diseases such as myocardial infarction and stroke.

KEYWORDS

Platelet - collagen - glycoprotein VI - α2β1 - thrombosis

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Mark L KahnM.D. 

Division of Cardiology and Department of Medicine, University of Pennsylvania

421 Curie Blvd., Room 952

Philadelphia, PA 19104

Email: markkahn@mail.med.upenn.edu