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Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke (GYPSIE) study results
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8765640/ https://www.ncbi.nlm.nih.gov/pubmed/35041713 http://dx.doi.org/10.1371/journal.pone.0262695 |
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author | Induruwa, Isuru McKinney, Harriet Kempster, Carly Thomas, Patrick Batista, Joana Malcor, Jean-Daniel Bonna, Arkadiusz McGee, Joanne Bumanlag-Amis, Elaine Rehnstrom, Karola Ashford, Sophie Soejima, Kenji Ouwehand, Willem Farndale, Richard Downes, Kate Warburton, Elizabeth Moroi, Masaaki Jung, Stephanie |
author_facet | Induruwa, Isuru McKinney, Harriet Kempster, Carly Thomas, Patrick Batista, Joana Malcor, Jean-Daniel Bonna, Arkadiusz McGee, Joanne Bumanlag-Amis, Elaine Rehnstrom, Karola Ashford, Sophie Soejima, Kenji Ouwehand, Willem Farndale, Richard Downes, Kate Warburton, Elizabeth Moroi, Masaaki Jung, Stephanie |
author_sort | Induruwa, Isuru |
collection | PubMed |
description | 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 [r(2) = 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. |
format | Online Article Text |
id | pubmed-8765640 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-87656402022-01-19 Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke (GYPSIE) study results Induruwa, Isuru McKinney, Harriet Kempster, Carly Thomas, Patrick Batista, Joana Malcor, Jean-Daniel Bonna, Arkadiusz McGee, Joanne Bumanlag-Amis, Elaine Rehnstrom, Karola Ashford, Sophie Soejima, Kenji Ouwehand, Willem Farndale, Richard Downes, Kate Warburton, Elizabeth Moroi, Masaaki Jung, Stephanie PLoS One Research Article 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 [r(2) = 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. Public Library of Science 2022-01-18 /pmc/articles/PMC8765640/ /pubmed/35041713 http://dx.doi.org/10.1371/journal.pone.0262695 Text en © 2022 Induruwa et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Induruwa, Isuru McKinney, Harriet Kempster, Carly Thomas, Patrick Batista, Joana Malcor, Jean-Daniel Bonna, Arkadiusz McGee, Joanne Bumanlag-Amis, Elaine Rehnstrom, Karola Ashford, Sophie Soejima, Kenji Ouwehand, Willem Farndale, Richard Downes, Kate Warburton, Elizabeth Moroi, Masaaki Jung, Stephanie Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke (GYPSIE) study results |
title | Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke (GYPSIE) study results |
title_full | Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke (GYPSIE) study results |
title_fullStr | Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke (GYPSIE) study results |
title_full_unstemmed | Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke (GYPSIE) study results |
title_short | Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke (GYPSIE) study results |
title_sort | platelet surface receptor glycoprotein vi-dimer is overexpressed in stroke: the glycoprotein vi in stroke (gypsie) study results |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8765640/ https://www.ncbi.nlm.nih.gov/pubmed/35041713 http://dx.doi.org/10.1371/journal.pone.0262695 |
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