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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...

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Autores principales: Haarmann, Axel, Vollmuth, Christoph, Kollikowski, Alexander M., Heuschmann, Peter U., Pham, Mirko, Stoll, Guido, Neugebauer, Hermann, Schuhmann, Michael K.
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
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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.
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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
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