Soluble Glycoprotein VI Levels Assessed Locally within the Extra- and Intracerebral Circulation in Hyper-Acute Thromboembolic Stroke: A Pilot Study
<b>Background:</b> Severe acute ischemic stroke (AIS) is mainly caused by thromboembolism originating from symptomatic carotid artery (ICA) stenosis or in the heart due to atrial fibrillation. Glycoprotein VI (GPVI), a principal platelet receptor, facilitates platelet adherence and throm...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-09-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/12/10/2191 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850204738537127936 |
|---|---|
| author | Andreas Starke Alexander M. Kollikowski Vivian Vogt Guido Stoll Bernhard Nieswandt Mirko Pham David Stegner Michael K. Schuhmann |
| author_facet | Andreas Starke Alexander M. Kollikowski Vivian Vogt Guido Stoll Bernhard Nieswandt Mirko Pham David Stegner Michael K. Schuhmann |
| author_sort | Andreas Starke |
| collection | DOAJ |
| description | <b>Background:</b> Severe acute ischemic stroke (AIS) is mainly caused by thromboembolism originating from symptomatic carotid artery (ICA) stenosis or in the heart due to atrial fibrillation. Glycoprotein VI (GPVI), a principal platelet receptor, facilitates platelet adherence and thrombus formation at sites of vascular injury such as symptomatic ICA stenosis. The shedding of GPVI from the platelet surface releases soluble GPVI (sGPVI) into the circulation. Here, we aimed to determine whether sGPVI can serve as a local biomarker to differentiate between local atherosclerotic and systemic cardiac thromboembolism in AIS. <b>Methods:</b> We conducted a cohort study involving 105 patients undergoing emergency endovascular thrombectomy (EVT) for anterior circulation stroke. First, sGPVI concentrations were measured in systemic arterial plasma samples collected at the ipsilateral ICA level, including groups with significantly (≥50%) stenotic and non-stenotic arteries. A second sample, taken from the intracerebral pial circulation, was used to assess GPVI shedding locally within the ischemic brain. <b>Results:</b> Our analysis revealed no significant increase in systemic sGPVI levels in patients with symptomatic ≥ 50% ICA stenosis (3.2 [95% CI 1.5–5.0] ng/mL; <i>n</i> = 33) compared with stroke patients without significant ICA stenosis (3.2 [95% CI 2.3–4.2] ng/mL; <i>n</i> = 72). Additionally, pial blood samples, reflecting intravascular molecular conditions during collateral flow, showed similar sGPVI levels when compared to the systemic ICA samples in both groups. <b>Conclusions:</b> Our findings indicate that GPVI is not locally cleaved and shed into the bloodstream in significant amounts during hyper-acute ischemic stroke, neither at the level of symptomatic ICA nor intracranially during collateral blood supply. Therefore, sGPVI does not appear to be suitable as a local stroke biomarker despite strong evidence of a major role for GPVI-signaling in stroke pathophysiology. |
| format | Article |
| id | doaj-art-f668caeb58f740a484fde12cd765f6f1 |
| institution | OA Journals |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-f668caeb58f740a484fde12cd765f6f12025-08-20T02:11:14ZengMDPI AGBiomedicines2227-90592024-09-011210219110.3390/biomedicines12102191Soluble Glycoprotein VI Levels Assessed Locally within the Extra- and Intracerebral Circulation in Hyper-Acute Thromboembolic Stroke: A Pilot StudyAndreas Starke0Alexander M. Kollikowski1Vivian Vogt2Guido Stoll3Bernhard Nieswandt4Mirko Pham5David Stegner6Michael K. Schuhmann7Rudolf Virchow Center for Integrative and Translational Imaging, Julius-Maximilians-Universität Würzburg (JMU), 97080 Würzburg, GermanyDepartment of Neuroradiology, University Hospital Würzburg, 97080 Würzburg, GermanyDepartment of Neurology, University Hospital Würzburg, 97080 Würzburg, GermanyInstitute for Experimental Biomedicine, University Hospital Würzburg, 97080 Würzburg, GermanyRudolf Virchow Center for Integrative and Translational Imaging, Julius-Maximilians-Universität Würzburg (JMU), 97080 Würzburg, GermanyDepartment of Neuroradiology, University Hospital Würzburg, 97080 Würzburg, GermanyRudolf Virchow Center for Integrative and Translational Imaging, Julius-Maximilians-Universität Würzburg (JMU), 97080 Würzburg, GermanyDepartment of Neurology, University Hospital Würzburg, 97080 Würzburg, Germany<b>Background:</b> Severe acute ischemic stroke (AIS) is mainly caused by thromboembolism originating from symptomatic carotid artery (ICA) stenosis or in the heart due to atrial fibrillation. Glycoprotein VI (GPVI), a principal platelet receptor, facilitates platelet adherence and thrombus formation at sites of vascular injury such as symptomatic ICA stenosis. The shedding of GPVI from the platelet surface releases soluble GPVI (sGPVI) into the circulation. Here, we aimed to determine whether sGPVI can serve as a local biomarker to differentiate between local atherosclerotic and systemic cardiac thromboembolism in AIS. <b>Methods:</b> We conducted a cohort study involving 105 patients undergoing emergency endovascular thrombectomy (EVT) for anterior circulation stroke. First, sGPVI concentrations were measured in systemic arterial plasma samples collected at the ipsilateral ICA level, including groups with significantly (≥50%) stenotic and non-stenotic arteries. A second sample, taken from the intracerebral pial circulation, was used to assess GPVI shedding locally within the ischemic brain. <b>Results:</b> Our analysis revealed no significant increase in systemic sGPVI levels in patients with symptomatic ≥ 50% ICA stenosis (3.2 [95% CI 1.5–5.0] ng/mL; <i>n</i> = 33) compared with stroke patients without significant ICA stenosis (3.2 [95% CI 2.3–4.2] ng/mL; <i>n</i> = 72). Additionally, pial blood samples, reflecting intravascular molecular conditions during collateral flow, showed similar sGPVI levels when compared to the systemic ICA samples in both groups. <b>Conclusions:</b> Our findings indicate that GPVI is not locally cleaved and shed into the bloodstream in significant amounts during hyper-acute ischemic stroke, neither at the level of symptomatic ICA nor intracranially during collateral blood supply. Therefore, sGPVI does not appear to be suitable as a local stroke biomarker despite strong evidence of a major role for GPVI-signaling in stroke pathophysiology.https://www.mdpi.com/2227-9059/12/10/2191blood plateletsGPVIstrokebiomarkercarotid artery stenosisthromboembolism |
| spellingShingle | Andreas Starke Alexander M. Kollikowski Vivian Vogt Guido Stoll Bernhard Nieswandt Mirko Pham David Stegner Michael K. Schuhmann Soluble Glycoprotein VI Levels Assessed Locally within the Extra- and Intracerebral Circulation in Hyper-Acute Thromboembolic Stroke: A Pilot Study Biomedicines blood platelets GPVI stroke biomarker carotid artery stenosis thromboembolism |
| title | Soluble Glycoprotein VI Levels Assessed Locally within the Extra- and Intracerebral Circulation in Hyper-Acute Thromboembolic Stroke: A Pilot Study |
| title_full | Soluble Glycoprotein VI Levels Assessed Locally within the Extra- and Intracerebral Circulation in Hyper-Acute Thromboembolic Stroke: A Pilot Study |
| title_fullStr | Soluble Glycoprotein VI Levels Assessed Locally within the Extra- and Intracerebral Circulation in Hyper-Acute Thromboembolic Stroke: A Pilot Study |
| title_full_unstemmed | Soluble Glycoprotein VI Levels Assessed Locally within the Extra- and Intracerebral Circulation in Hyper-Acute Thromboembolic Stroke: A Pilot Study |
| title_short | Soluble Glycoprotein VI Levels Assessed Locally within the Extra- and Intracerebral Circulation in Hyper-Acute Thromboembolic Stroke: A Pilot Study |
| title_sort | soluble glycoprotein vi levels assessed locally within the extra and intracerebral circulation in hyper acute thromboembolic stroke a pilot study |
| topic | blood platelets GPVI stroke biomarker carotid artery stenosis thromboembolism |
| url | https://www.mdpi.com/2227-9059/12/10/2191 |
| work_keys_str_mv | AT andreasstarke solubleglycoproteinvilevelsassessedlocallywithintheextraandintracerebralcirculationinhyperacutethromboembolicstrokeapilotstudy AT alexandermkollikowski solubleglycoproteinvilevelsassessedlocallywithintheextraandintracerebralcirculationinhyperacutethromboembolicstrokeapilotstudy AT vivianvogt solubleglycoproteinvilevelsassessedlocallywithintheextraandintracerebralcirculationinhyperacutethromboembolicstrokeapilotstudy AT guidostoll solubleglycoproteinvilevelsassessedlocallywithintheextraandintracerebralcirculationinhyperacutethromboembolicstrokeapilotstudy AT bernhardnieswandt solubleglycoproteinvilevelsassessedlocallywithintheextraandintracerebralcirculationinhyperacutethromboembolicstrokeapilotstudy AT mirkopham solubleglycoproteinvilevelsassessedlocallywithintheextraandintracerebralcirculationinhyperacutethromboembolicstrokeapilotstudy AT davidstegner solubleglycoproteinvilevelsassessedlocallywithintheextraandintracerebralcirculationinhyperacutethromboembolicstrokeapilotstudy AT michaelkschuhmann solubleglycoproteinvilevelsassessedlocallywithintheextraandintracerebralcirculationinhyperacutethromboembolicstrokeapilotstudy |