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Endothelial dysfunction is a hallmark of chronic kidney disease (CKD), but its mechanisms are poorly understood. We hypothesized that CKD disrupts endothelial mechanics in an MR\/ENaC-dependent process. Methods: Primary human endothelial cells were cultured with uremic serum derived from children with stage 3\u20135 (predialysis) CKD or adult hemodialysis (HD) patients or healthy controls. The height and stiffness of the endothelial glycocalyx (eGC) and cortex were monitored by atomic force microscopy (AFM) using an ultrasensitive mechanical nanosensor. Results: In a stage-dependent manner, sera from children with CKD induced a significant increase in eGC and cortex stiffness and an incremental reduction of the eGC height. AFM measurements were significantly associated with individual pulse wave velocity and serum concentrations of gut-derived uremic toxins. Serum from HD patients increased MR expression and mechanical stiffness of the endothelial cortex, an effect reversed by MR and ENaC antagonists, decreased eNOS expression and NO bioavailability, and augmented monocyte adhesion. Conclusion: These data indicate progressive structural damage of the endothelial surface with diminishing kidney function and identify the MR as a mediator of CKD-induced endothelial dysfunction.<\/jats:p>","DOI":"10.3390\/ijms231810659","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T21:06:52Z","timestamp":1663103212000},"page":"10659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Effects of Chronic Kidney Disease on Nanomechanics of the Endothelial Glycocalyx Are Mediated by the Mineralocorticoid Receptor"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5597-5751","authenticated-orcid":false,"given":"Benedikt","family":"Fels","sequence":"first","affiliation":[{"name":"Institute of Physiology, University of Luebeck, D23562 Luebeck, Germany"},{"name":"DZHK (German Research Centre for Cardiovascular Research), Partner Site Hamburg\/Luebeck\/Kiel, D23562 Luebeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Beyer","sequence":"additional","affiliation":[{"name":"Institute of Physiology II, University of Muenster, D48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violeta","family":"Caza\u00f1a-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Instituto de Tecnolog\u00edas Biom\u00e9dicas, Universidad de La Laguna, ES38206 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Giraldez","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Instituto de Tecnolog\u00edas Biom\u00e9dicas, Universidad de La Laguna, ES38206 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5015-7474","authenticated-orcid":false,"given":"Juan","family":"Navarro-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Instituto de Tecnolog\u00edas Biom\u00e9dicas, Universidad de La Laguna, ES38206 La Laguna, Spain"},{"name":"Unidad de Investigaci\u00f3n and Servicio de Nefrolog\u00eda, Hospital Universitario Nuestra Se\u00f1ora de Candelaria, ES38010 Santa Cruz de Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4324-2793","authenticated-orcid":false,"given":"Diego","family":"Alvarez de la Rosa","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Instituto de Tecnolog\u00edas Biom\u00e9dicas, Universidad de La Laguna, ES38206 La Laguna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7564-9937","authenticated-orcid":false,"given":"Franz","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Division, Center for Pediatrics and Adolescent Medicine, University of Heidelberg, D69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2644-5628","authenticated-orcid":false,"given":"Aysun","family":"Bayazit","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Cukurova University, Adana TR01250, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0141ukasz","family":"Obrycki","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kidney Transplantation and Hypertension, Children\u2019s Memorial Health Institute, PL04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Ranchin","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Unit, H\u00f4pital Femme M\u00e8re Enfant, Hospices Civils de Lyon, Universit\u00e9 de Lyon, F69002 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8032-4096","authenticated-orcid":false,"given":"Johannes","family":"Holle","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Nephrology and Metabolic Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, D13353 Berlin, Germany"},{"name":"DZHK (German Research Centre for Cardiovascular Research), Partner Site Berlin, D10785 Berlin, 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