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


Type
Article
Change log
Authors
McKinney, Harriet 
Kempster, Carly 
Thomas, Patrick 
Batista, Joana 
Abstract

OBJECTIVES: Platelet 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. METHODS: 129 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). RESULTS: The platelets of stroke patients expressed significantly higher total GPVI and GPVI-dimer (P<0.0001) as well as demonstrating higher resting P-selectin exposure (P<0.0001), a measure of platelet activity, compared to the control group, suggesting increased circulating platelet activation. GPVI-dimer expression was strongly correlated circulating platelet activation [r2 = 0.88, P<0.0001] in stroke patients. Furthermore, higher platelet surface GPVI expression was associated with increased stroke severity at admission. At day-90 post-stroke, GPVI-dimer expression and was further raised compared to the level at admission (P<0.0001) despite anti-thrombotic therapy. All ischemic stroke subtypes and hemorrhagic strokes expressed significantly higher GPVI-dimer compared to controls (P<0.0001). CONCLUSIONS: Stroke 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.

Description
Keywords
Aged, Aged, 80 and over, Biomarkers, Case-Control Studies, Female, Follow-Up Studies, Humans, Male, Middle Aged, Platelet Activation, Platelet Adhesiveness, Platelet Membrane Glycoproteins, Prognosis, Protein Multimerization, Stroke
Journal Title
PLoS One
Conference Name
Journal ISSN
1932-6203
1932-6203
Volume Title
17
Publisher
Public Library of Science (PLoS)
Sponsorship
British Heart Foundation (None)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Cambridge University Hospitals NHS Foundation Trust (CUH) (Unknown)
British Heart Foundation, SP/13/7/30575, Dr Stephanie M Jung British Heart Foundation, RE/13/6/30180, Dr Isuru Induruwa NIHR CL to Dr Isuru Induruwa