PLoS ONE (Jan 2022)

Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke (GYPSIE) study results.

  • Isuru Induruwa,
  • Harriet McKinney,
  • Carly Kempster,
  • Patrick Thomas,
  • Joana Batista,
  • Jean-Daniel Malcor,
  • Arkadiusz Bonna,
  • Joanne McGee,
  • Elaine Bumanlag-Amis,
  • Karola Rehnstrom,
  • Sophie Ashford,
  • Kenji Soejima,
  • Willem Ouwehand,
  • Richard Farndale,
  • Kate Downes,
  • Elizabeth Warburton,
  • Masaaki Moroi,
  • Stephanie Jung

DOI
https://doi.org/10.1371/journal.pone.0262695
Journal volume & issue
Vol. 17, no. 1
p. e0262695

Abstract

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ObjectivesPlatelet activation underpins thrombus formation in ischemic stroke. The active, dimeric form of platelet receptor glycoprotein (GP) VI plays key roles by binding platelet ligands collagen and fibrin, leading to platelet activation. We investigated whether patients presenting with stroke expressed more GPVI on their platelet surface and had more active circulating platelets as measured by platelet P-selectin exposure.Methods129 ischemic or hemorrhagic stroke patients were recruited within 8h of symptom onset. Whole blood was analyzed for platelet-surface expression of total GPVI, GPVI-dimer, and P-selectin by flow cytometry at admission and day-90 post-stroke. Results were compared against a healthy control population (n = 301).ResultsThe platelets of stroke patients expressed significantly higher total GPVI and GPVI-dimer (PConclusionsStroke patients express more GPVI-dimer on their platelet surface at presentation, lasting at least until day-90 post-stroke. Small molecule GPVI-dimer inhibitors are currently in development and the results of this study validate that GPVI-dimer as an anti-thrombotic target in ischemic stroke.