The role of the platelet in the pathogenesis of atherothrombosis

Steven R. Steinhubl, David J. Moliterno

Research output: Contribution to journalReview articlepeer-review

127 Scopus citations

Abstract

Platelet adhesion, activation, and aggregation at sites of vascular endothelial disruption caused by atherosclerosis are key events in arterial thrombus formation. Platelet tethering and adhesion to the arterial wall, particularly under high shear forces, are achieved through multiple high-affinity interactions between platelet membrane receptors (integrins) and ligands within the exposed subendothelium, most notably collagen and von Willebrand factor (vWF). Platelet adhesion to collagen occurs both indirectly, via binding of the platelet glycoprotein (GP) Ib-V-IX receptor to circulating vWF, which binds to exposed collagen, and directly, via interaction with the platelet receptors GP VI and GP Ia/IIb. Platelet activation, initiated by exposed collagen and locally generated soluble platelet agonists (primarily thrombin, ADP, and thromboxane A2), provides the stimulus for the release of platelet-derived growth factors, adhesion molecules and coagulation factors, activation of adjacent platelets, and conformational changes in the platelet αIIbβ3 integrin (GP IIb/IIIa receptor). Platelet aggregation, mediated primarily by interaction between the activated platelet GP IIb/IIIa receptor and its ligands, fibrinogen and vWF, results in the formation of a platelet-rich thrombus. Currently available antiplatelet drugs (aspirin [acetylsalicylic acid], dipyridamole, clopidogrel, ticlopidine, abciximab, eptifibatide, tirofiban) act on specific targets to inhibit platelet activation and aggregation. Elucidation of the multiple mechanisms involved in platelet thrombus formation provides opportunities for selectively inhibiting the pathways most relevant to the pathophysiology of atherothrombosis.

Original languageEnglish
Pages (from-to)399-408
Number of pages10
JournalAmerican Journal of Cardiovascular Drugs
Volume5
Issue number6
DOIs
StatePublished - 2005

Bibliographical note

Funding Information:
The authors would like to thank Andrew Fitton for editorial support in the preparation of the manuscript. This assistance was funded by Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership.

Funding Information:
Dr Moliterno receives grant support from Guilford Pharmaceuticals Inc. Dr Steinhubl is a consultant for, and receives grant support from, Bristol-Myers Squibb Co., Sanofi-Aventis, The Medicines Company, and Ac-cumetrics Inc.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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