Targeting glycoprotein VI and the immunoreceptor tyrosine-based activation motif signaling pathway

Arterioscler Thromb Vasc Biol. 2014 Aug;34(8):1615-20. doi: 10.1161/ATVBAHA.114.303408. Epub 2014 Jun 12.

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.

Keywords: antiplatelet agents; immunoreceptor tyrosine-based activation motif; platelet inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Drug Design*
  • Hemorrhage / chemically induced
  • Hemostasis / drug effects
  • Humans
  • Immunoreceptor Tyrosine-Based Inhibition Motif*
  • Molecular Targeted Therapy*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Membrane Glycoproteins / antagonists & inhibitors*
  • Platelet Membrane Glycoproteins / chemistry
  • Platelet Membrane Glycoproteins / metabolism
  • Protein Conformation
  • Signal Transduction / drug effects*
  • Thrombosis / blood
  • Thrombosis / drug therapy

Substances

  • Platelet Aggregation Inhibitors
  • Platelet Membrane Glycoproteins
  • platelet membrane glycoprotein VI