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ATVB in Focus: New Targets of Antiplatelet Drug Development

Targeting Glycoprotein VI and the Immunoreceptor Tyrosine-Based Activation Motif Signaling Pathway

David Stegner, Elizabeth J. Haining, Bernhard Nieswandt
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https://doi.org/10.1161/ATVBAHA.114.303408
Arteriosclerosis, Thrombosis, and Vascular Biology. 2014;34:1615-1620
Originally published June 12, 2014
David Stegner
From the Department of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.
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Elizabeth J. Haining
From the Department of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.
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Bernhard Nieswandt
From the Department of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.
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This article has a correction. Please see:

  • Correction - April 01, 2015
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  • Article
    • Abstract
    • Structure and Signaling of GPVI
    • Fcγ Receptor IIA
    • C-Type Lectin-Like Receptor 2
    • GPVI in Thromboinflammation
    • Blocking the Collagen–GPVI Interaction
    • Targeted Removal of GPVI From the Cell Surface
    • Targeting (hem)ITAM Signaling
    • Conclusions
    • Acknowledgments
    • Sources of Funding
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Abstract

Coronary artery thrombosis and ischemic stroke are often initiated by the disruption of an atherosclerotic plaque and consequent intravascular platelet activation. Thus, antiplatelet drugs are central in the treatment and prevention of the initial, and subsequent, vascular events. However, novel pharmacological targets for platelet inhibition remain an important goal of cardiovascular research because of the negative effect of existing antiplatelet drugs on primary hemostasis. One promising target is the platelet collagen receptor glycoprotein VI. Blockade or antibody-mediated depletion of this receptor in circulating platelets is beneficial in experimental models of thrombosis and thrombo-inflammatory diseases, such as stroke, without impairing hemostasis. In this review, we summarize the importance of glycoprotein VI and (hem)immunoreceptor tyrosine-based activation motif signaling in hemostasis, thrombosis, and thrombo-inflammatory processes and discuss the targeting strategies currently under development for inhibiting glycoprotein VI and its signaling.

  • antiplatelet agents
  • immunoreceptor tyrosine-based activation motif
  • platelet inhibitors
  • Received April 11, 2014.
  • Accepted May 28, 2014.
  • © 2014 American Heart Association, Inc.
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Arteriosclerosis, Thrombosis, and Vascular Biology
August 2014, Volume 34, Issue 8
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  • Article
    • Abstract
    • Structure and Signaling of GPVI
    • Fcγ Receptor IIA
    • C-Type Lectin-Like Receptor 2
    • GPVI in Thromboinflammation
    • Blocking the Collagen–GPVI Interaction
    • Targeted Removal of GPVI From the Cell Surface
    • Targeting (hem)ITAM Signaling
    • Conclusions
    • Acknowledgments
    • Sources of Funding
    • Disclosures
    • References
  • Figures & Tables
  • Info & Metrics
  • eLetters

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    Targeting Glycoprotein VI and the Immunoreceptor Tyrosine-Based Activation Motif Signaling Pathway
    David Stegner, Elizabeth J. Haining and Bernhard Nieswandt
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2014;34:1615-1620, originally published June 12, 2014
    https://doi.org/10.1161/ATVBAHA.114.303408

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    Targeting Glycoprotein VI and the Immunoreceptor Tyrosine-Based Activation Motif Signaling Pathway
    David Stegner, Elizabeth J. Haining and Bernhard Nieswandt
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2014;34:1615-1620, originally published June 12, 2014
    https://doi.org/10.1161/ATVBAHA.114.303408
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