{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T03:19:25Z","timestamp":1773199165632,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["376777"],"award-info":[{"award-number":["376777"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Hemolytic uremic syndrome (HUS) is a rare disease primarily characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Endothelial damage is the hallmark of the pathogenesis of HUS with an infection with the Shiga toxin (Stx) producing Escherichia coli (STEC-HUS) as the main underlying cause in childhood. In this study, blood outgrowth endothelial cells (BOECs) were isolated from healthy donors serving as controls and patients recovered from STEC-HUS. We hypothesized that Stx is more cytotoxic for STEC-HUS BOECs compared to healthy donor control BOECs explained via a higher amount of Stx bound to the cell surface. Binding of Shiga toxin-2a (Stx2a) was investigated and the effect on cytotoxicity, protein synthesis, wound healing, and cell proliferation was studied in static conditions. Results show that BOECs are highly susceptible for Stx2a. Stx2a is able to bind to the cell surface of BOECs with cytotoxicity in a dose-dependent manner as a result. Pre-treatment with tumor necrosis factor alpha (TNF-\u03b1) results in enhanced Stx binding with 20\u201330% increased lactate dehydrogenase (LDH) release. Endothelial wound healing is delayed in a Stx2a-rich environment; however, this is not caused by an effect on the proliferation rate of BOECs. No significant differences were found between control BOECs and BOECs from recovered STEC-HUS patients in terms of Stx2a binding and inhibition of protein synthesis.<\/jats:p>","DOI":"10.3390\/toxins12080483","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T12:15:38Z","timestamp":1596111338000},"page":"483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Primary Human Derived Blood Outgrowth Endothelial Cells: An Appropriate In Vitro Model to Study Shiga Toxin Mediated Damage of Endothelial Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"Wouter J. C.","family":"Feitz","sequence":"first","affiliation":[{"name":"Department of Pediatric Nephrology, Amalia Children\u2019s Hospital, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands"},{"name":"Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1990-1189","authenticated-orcid":false,"given":"Nicole C. A. J.","family":"van de Kar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Amalia Children\u2019s Hospital, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Cheong","sequence":"additional","affiliation":[{"name":"Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thea J. A. M.","family":"van der Velden","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Amalia Children\u2019s Hospital, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina G.","family":"Ortiz-Sandoval","sequence":"additional","affiliation":[{"name":"Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothea","family":"Orth-H\u00f6ller","sequence":"additional","affiliation":[{"name":"Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lambert P. J. W.","family":"van den Heuvel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Amalia Children\u2019s Hospital, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands"},{"name":"Department of Development and Regeneration, Department of Pediatric Nephrology, KU, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4168-3277","authenticated-orcid":false,"given":"Christoph","family":"Licht","sequence":"additional","affiliation":[{"name":"Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"},{"name":"Division of Nephrology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada"},{"name":"Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/s41581-018-0098-z","article-title":"Endothelium structure and function in kidney health and disease","volume":"15","author":"Fakhouri","year":"2019","journal-title":"Nat. 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