Cargando…
Vasoactive Soluble Endoglin: A Novel Biomarker Indicative of Reperfusion after Cerebral Large-Vessel Occlusion
Now that mechanical thrombectomy has substantially improved outcomes after large-vessel occlusion stroke in up to every second patient, futile reperfusion wherein successful recanalization is not followed by a favorable outcome is moving into focus. Unfortunately, blood-based biomarkers, which ident...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856463/ https://www.ncbi.nlm.nih.gov/pubmed/36672223 http://dx.doi.org/10.3390/cells12020288 |
_version_ | 1784873636271751168 |
---|---|
author | Haarmann, Axel Vollmuth, Christoph Kollikowski, Alexander M. Heuschmann, Peter U. Pham, Mirko Stoll, Guido Neugebauer, Hermann Schuhmann, Michael K. |
author_facet | Haarmann, Axel Vollmuth, Christoph Kollikowski, Alexander M. Heuschmann, Peter U. Pham, Mirko Stoll, Guido Neugebauer, Hermann Schuhmann, Michael K. |
author_sort | Haarmann, Axel |
collection | PubMed |
description | Now that mechanical thrombectomy has substantially improved outcomes after large-vessel occlusion stroke in up to every second patient, futile reperfusion wherein successful recanalization is not followed by a favorable outcome is moving into focus. Unfortunately, blood-based biomarkers, which identify critical stages of hemodynamically compromised yet reperfused tissue, are lacking. We recently reported that hypoxia induces the expression of endoglin, a TGF-β co-receptor, in human brain endothelium in vitro. Subsequent reoxygenation resulted in shedding. Our cell model suggests that soluble endoglin compromises the brain endothelial barrier function. To evaluate soluble endoglin as a potential biomarker of reperfusion (-injury) we analyzed its concentration in 148 blood samples of patients with acute stroke due to large-vessel occlusion. In line with our in vitro data, systemic soluble endoglin concentrations were significantly higher in patients with successful recanalization, whereas hypoxia alone did not induce local endoglin shedding, as analyzed by intra-arterial samples from hypoxic vasculature. In patients with reperfusion, higher concentrations of soluble endoglin additionally indicated larger infarct volumes at admission. In summary, we give translational evidence that the sequence of hypoxia and subsequent reoxygenation triggers the release of vasoactive soluble endoglin in large-vessel occlusion stroke and can serve as a biomarker for severe ischemia with ensuing recanalization/reperfusion. |
format | Online Article Text |
id | pubmed-9856463 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98564632023-01-21 Vasoactive Soluble Endoglin: A Novel Biomarker Indicative of Reperfusion after Cerebral Large-Vessel Occlusion Haarmann, Axel Vollmuth, Christoph Kollikowski, Alexander M. Heuschmann, Peter U. Pham, Mirko Stoll, Guido Neugebauer, Hermann Schuhmann, Michael K. Cells Communication Now that mechanical thrombectomy has substantially improved outcomes after large-vessel occlusion stroke in up to every second patient, futile reperfusion wherein successful recanalization is not followed by a favorable outcome is moving into focus. Unfortunately, blood-based biomarkers, which identify critical stages of hemodynamically compromised yet reperfused tissue, are lacking. We recently reported that hypoxia induces the expression of endoglin, a TGF-β co-receptor, in human brain endothelium in vitro. Subsequent reoxygenation resulted in shedding. Our cell model suggests that soluble endoglin compromises the brain endothelial barrier function. To evaluate soluble endoglin as a potential biomarker of reperfusion (-injury) we analyzed its concentration in 148 blood samples of patients with acute stroke due to large-vessel occlusion. In line with our in vitro data, systemic soluble endoglin concentrations were significantly higher in patients with successful recanalization, whereas hypoxia alone did not induce local endoglin shedding, as analyzed by intra-arterial samples from hypoxic vasculature. In patients with reperfusion, higher concentrations of soluble endoglin additionally indicated larger infarct volumes at admission. In summary, we give translational evidence that the sequence of hypoxia and subsequent reoxygenation triggers the release of vasoactive soluble endoglin in large-vessel occlusion stroke and can serve as a biomarker for severe ischemia with ensuing recanalization/reperfusion. MDPI 2023-01-11 /pmc/articles/PMC9856463/ /pubmed/36672223 http://dx.doi.org/10.3390/cells12020288 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Haarmann, Axel Vollmuth, Christoph Kollikowski, Alexander M. Heuschmann, Peter U. Pham, Mirko Stoll, Guido Neugebauer, Hermann Schuhmann, Michael K. Vasoactive Soluble Endoglin: A Novel Biomarker Indicative of Reperfusion after Cerebral Large-Vessel Occlusion |
title | Vasoactive Soluble Endoglin: A Novel Biomarker Indicative of Reperfusion after Cerebral Large-Vessel Occlusion |
title_full | Vasoactive Soluble Endoglin: A Novel Biomarker Indicative of Reperfusion after Cerebral Large-Vessel Occlusion |
title_fullStr | Vasoactive Soluble Endoglin: A Novel Biomarker Indicative of Reperfusion after Cerebral Large-Vessel Occlusion |
title_full_unstemmed | Vasoactive Soluble Endoglin: A Novel Biomarker Indicative of Reperfusion after Cerebral Large-Vessel Occlusion |
title_short | Vasoactive Soluble Endoglin: A Novel Biomarker Indicative of Reperfusion after Cerebral Large-Vessel Occlusion |
title_sort | vasoactive soluble endoglin: a novel biomarker indicative of reperfusion after cerebral large-vessel occlusion |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856463/ https://www.ncbi.nlm.nih.gov/pubmed/36672223 http://dx.doi.org/10.3390/cells12020288 |
work_keys_str_mv | AT haarmannaxel vasoactivesolubleendoglinanovelbiomarkerindicativeofreperfusionaftercerebrallargevesselocclusion AT vollmuthchristoph vasoactivesolubleendoglinanovelbiomarkerindicativeofreperfusionaftercerebrallargevesselocclusion AT kollikowskialexanderm vasoactivesolubleendoglinanovelbiomarkerindicativeofreperfusionaftercerebrallargevesselocclusion AT heuschmannpeteru vasoactivesolubleendoglinanovelbiomarkerindicativeofreperfusionaftercerebrallargevesselocclusion AT phammirko vasoactivesolubleendoglinanovelbiomarkerindicativeofreperfusionaftercerebrallargevesselocclusion AT stollguido vasoactivesolubleendoglinanovelbiomarkerindicativeofreperfusionaftercerebrallargevesselocclusion AT neugebauerhermann vasoactivesolubleendoglinanovelbiomarkerindicativeofreperfusionaftercerebrallargevesselocclusion AT schuhmannmichaelk vasoactivesolubleendoglinanovelbiomarkerindicativeofreperfusionaftercerebrallargevesselocclusion |