Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke
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 m...
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| Veröffentlicht in: | PloS one 2022-01, Vol.17 (1), p.e0262695 |
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| creator | 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 |
| description | 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. 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). The platelets of stroke patients expressed significantly higher total GPVI and GPVI-dimer (P |
| doi_str_mv | 10.1371/journal.pone.0262695 |
| format | Article |
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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. 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). 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.sup.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). 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><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0262695</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>Activation ; Blood platelets ; Development and progression ; Glycoproteins ; Health aspects ; Physiological aspects ; Stroke (Disease)</subject><ispartof>PloS one, 2022-01, Vol.17 (1), p.e0262695</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids></links><search><creatorcontrib>Induruwa, Isuru</creatorcontrib><creatorcontrib>McKinney, Harriet</creatorcontrib><creatorcontrib>Kempster, Carly</creatorcontrib><creatorcontrib>Thomas, Patrick</creatorcontrib><creatorcontrib>Batista, Joana</creatorcontrib><creatorcontrib>Malcor, Jean-Daniel</creatorcontrib><creatorcontrib>Bonna, Arkadiusz</creatorcontrib><creatorcontrib>McGee, Joanne</creatorcontrib><creatorcontrib>Bumanlag-Amis, Elaine</creatorcontrib><creatorcontrib>Rehnstrom, Karola</creatorcontrib><creatorcontrib>Ashford, Sophie</creatorcontrib><creatorcontrib>Soejima, Kenji</creatorcontrib><creatorcontrib>Ouwehand, Willem</creatorcontrib><creatorcontrib>Farndale, Richard</creatorcontrib><creatorcontrib>Downes, Kate</creatorcontrib><creatorcontrib>Warburton, Elizabeth</creatorcontrib><creatorcontrib>Moroi, Masaaki</creatorcontrib><creatorcontrib>Jung, Stephanie</creatorcontrib><title>Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke</title><title>PloS one</title><description>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. 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). 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.sup.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). 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><subject>Activation</subject><subject>Blood platelets</subject><subject>Development and progression</subject><subject>Glycoproteins</subject><subject>Health aspects</subject><subject>Physiological aspects</subject><subject>Stroke (Disease)</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNqFjE9LwzAchoMoOKffwENOgofWtGmSxtsYOgeDiRu7jiz9peuMTUlSmd_ev4ft5Ol94XneF6HrjKQZFdndzvW-VTbtXAspyXnOJTtBg0zSPOE5oacH_RxdhLAjhNGS8wFqnq2KYCHi0HujNGAPGrroPK7th3addxGaFq-mSdW8gcdNwO4dPOw7DyFAhb9giN69wj1ebgFPjlffePGDL9GZUTbA1V8O0fLxYTl-SmbzyXQ8miW1lDzRORWGlFwqZiqVq4IVshCF0ISJQpVGG26EKVhFKNlUG0YzsSFU8hyEUYZROkS3v7e1srBuWu3aCPtYqz6E9XTxsh7xUpZU0oz_485Xx-7NgbsFZeM2ONvHxrXhUPwEN_B52w</recordid><startdate>20220118</startdate><enddate>20220118</enddate><creator>Induruwa, Isuru</creator><creator>McKinney, Harriet</creator><creator>Kempster, Carly</creator><creator>Thomas, Patrick</creator><creator>Batista, Joana</creator><creator>Malcor, Jean-Daniel</creator><creator>Bonna, Arkadiusz</creator><creator>McGee, Joanne</creator><creator>Bumanlag-Amis, Elaine</creator><creator>Rehnstrom, Karola</creator><creator>Ashford, Sophie</creator><creator>Soejima, Kenji</creator><creator>Ouwehand, Willem</creator><creator>Farndale, Richard</creator><creator>Downes, Kate</creator><creator>Warburton, Elizabeth</creator><creator>Moroi, Masaaki</creator><creator>Jung, Stephanie</creator><general>Public Library of Science</general><scope>IOV</scope><scope>ISR</scope></search><sort><creationdate>20220118</creationdate><title>Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke</title><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g996-c237f0869a5fda2a45494747c0574a8fcf6f7f45d030bdb5317b03962e7faf533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Activation</topic><topic>Blood platelets</topic><topic>Development and progression</topic><topic>Glycoproteins</topic><topic>Health aspects</topic><topic>Physiological aspects</topic><topic>Stroke (Disease)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Induruwa, Isuru</creatorcontrib><creatorcontrib>McKinney, Harriet</creatorcontrib><creatorcontrib>Kempster, Carly</creatorcontrib><creatorcontrib>Thomas, Patrick</creatorcontrib><creatorcontrib>Batista, Joana</creatorcontrib><creatorcontrib>Malcor, Jean-Daniel</creatorcontrib><creatorcontrib>Bonna, Arkadiusz</creatorcontrib><creatorcontrib>McGee, Joanne</creatorcontrib><creatorcontrib>Bumanlag-Amis, Elaine</creatorcontrib><creatorcontrib>Rehnstrom, Karola</creatorcontrib><creatorcontrib>Ashford, Sophie</creatorcontrib><creatorcontrib>Soejima, Kenji</creatorcontrib><creatorcontrib>Ouwehand, Willem</creatorcontrib><creatorcontrib>Farndale, Richard</creatorcontrib><creatorcontrib>Downes, Kate</creatorcontrib><creatorcontrib>Warburton, Elizabeth</creatorcontrib><creatorcontrib>Moroi, Masaaki</creatorcontrib><creatorcontrib>Jung, Stephanie</creatorcontrib><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Induruwa, Isuru</au><au>McKinney, Harriet</au><au>Kempster, Carly</au><au>Thomas, Patrick</au><au>Batista, Joana</au><au>Malcor, Jean-Daniel</au><au>Bonna, Arkadiusz</au><au>McGee, Joanne</au><au>Bumanlag-Amis, Elaine</au><au>Rehnstrom, Karola</au><au>Ashford, Sophie</au><au>Soejima, Kenji</au><au>Ouwehand, Willem</au><au>Farndale, Richard</au><au>Downes, Kate</au><au>Warburton, Elizabeth</au><au>Moroi, Masaaki</au><au>Jung, Stephanie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke</atitle><jtitle>PloS one</jtitle><date>2022-01-18</date><risdate>2022</risdate><volume>17</volume><issue>1</issue><spage>e0262695</spage><pages>e0262695-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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. 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). 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.sup.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). 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.</abstract><pub>Public Library of Science</pub><doi>10.1371/journal.pone.0262695</doi><tpages>e0262695</tpages></addata></record> |
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| subjects | Activation Blood platelets Development and progression Glycoproteins Health aspects Physiological aspects Stroke (Disease) |
| title | Platelet surface receptor glycoprotein VI-dimer is overexpressed in stroke: The Glycoprotein VI in Stroke |
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