{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T18:42:27Z","timestamp":1778092947871,"version":"3.51.4"},"reference-count":12,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Stiftung Neurologie","award":["374031971\u2013CRC\/TR 240"],"award-info":[{"award-number":["374031971\u2013CRC\/TR 240"]}]},{"name":"Deutsche Stiftung Neurologie","award":["413657723"],"award-info":[{"award-number":["413657723"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["374031971\u2013CRC\/TR 240"],"award-info":[{"award-number":["374031971\u2013CRC\/TR 240"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["413657723"],"award-info":[{"award-number":["413657723"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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-\u03b2 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.<\/jats:p>","DOI":"10.3390\/cells12020288","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T02:28:44Z","timestamp":1673490524000},"page":"288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Vasoactive Soluble Endoglin: A Novel Biomarker Indicative of Reperfusion after Cerebral Large-Vessel Occlusion"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5597-6225","authenticated-orcid":false,"given":"Axel","family":"Haarmann","sequence":"first","affiliation":[{"name":"Department of Neurology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5893-1196","authenticated-orcid":false,"given":"Christoph","family":"Vollmuth","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0288-5928","authenticated-orcid":false,"given":"Alexander M.","family":"Kollikowski","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter U.","family":"Heuschmann","sequence":"additional","affiliation":[{"name":"Institute of Clinical Epidemiology and Biometry, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"},{"name":"Clinical Trial Center, University Hospital W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirko","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2474-5165","authenticated-orcid":false,"given":"Guido","family":"Stoll","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermann","family":"Neugebauer","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael K.","family":"Schuhmann","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41582-019-0221-1","article-title":"Thrombo-inflammation in acute ischaemic stroke\u2014Implications for treatment","volume":"15","author":"Stoll","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dagonnier, M., Donnan, G.A., Davis, S.M., Dewey, H.M., and Howells, D.W. (2021). Acute Stroke Biomarkers: Are We There Yet?. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.619721"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Haarmann, A., Zimmermann, L., Bieber, M., Silwedel, C., Stoll, G., and Schuhmann, M.K. (2022). Regulation and Release of Vasoactive Endoglin by Brain Endothelium in Response to Hypoxia\/Reoxygenation in Stroke. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137085"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1002\/ana.25665","article-title":"Local Leukocyte Invasion during Hyperacute Human Ischemic Stroke","volume":"87","author":"Kollikowski","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1016\/S0140-6736(00)02237-6","article-title":"Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. ASPECTS Study Group. Alberta Stroke Programme Early CT Score","volume":"355","author":"Barber","year":"2000","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bellut, M., Raimondi, A.T., Haarmann, A., Zimmermann, L., Stoll, G., and Schuhmann, M.K. (2022). NLRP3 Inhibition Reduces rt-PA Induced Endothelial Dysfunction under Ischemic Conditions. Biomedicines, 10.","DOI":"10.3390\/biomedicines10040762"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1001\/jamaneurol.2021.0065","article-title":"Local Cerebral Recombinant Tissue Plasminogen Activator Concentrations During Acute Stroke","volume":"78","author":"Essig","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.bbrc.2009.12.170","article-title":"Endothelial cells are activated during hypoxia via endoglin\/ALK-1\/SMAD1\/5 signaling in vivo and in vitro","volume":"392","author":"Tian","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1093\/brain\/123.4.687","article-title":"Cytokine-induced modulation of cellular adhesion to human cerebral endothelial cells is mediated by soluble vascular cell adhesion molecule-1","volume":"123","author":"Kallmann","year":"2000","journal-title":"Brain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s00401-015-1417-0","article-title":"Soluble VCAM-1 impairs human brain endothelial barrier integrity via integrin alpha-4-transduced outside-in signalling","volume":"129","author":"Haarmann","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1177\/0271678X221105764","article-title":"An intravascular perspective on hyper-acute neutrophil, T-cell and platelet responses: Similarities between human and experimental stroke","volume":"42","author":"Stoll","year":"2022","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1007\/s00018-017-2694-7","article-title":"Human endoglin as a potential new partner involved in platelet-endothelium interactions","volume":"75","author":"Rossi","year":"2018","journal-title":"Cell. Mol. Life Sci."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/2\/288\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:03:27Z","timestamp":1760119407000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/2\/288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,11]]},"references-count":12,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["cells12020288"],"URL":"https:\/\/doi.org\/10.3390\/cells12020288","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,11]]}}}