{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T06:26:32Z","timestamp":1793427992277,"version":"4.5.0"},"reference-count":99,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,5]],"date-time":"2020-04-05T00:00:00Z","timestamp":1586044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Chronic kidney disease (CKD) is associated with a high prevalence of cardiovascular diseases. During CKD, the uremic toxin indoxyl sulfate (IS)\u2014derived from tryptophan metabolism\u2014accumulates. IS is involved in the pathophysiology of cardiovascular complications. IS can be described as an endotheliotoxin: IS induces endothelial dysfunction implicated in cardiovascular morbidity and mortality during CKD. In this review, we describe clinical and experimental evidence for IS endothelial toxicity and focus on the various molecular pathways implicated. In patients with CKD, plasma concentrations of IS correlate with cardiovascular events and mortality, with vascular calcification and atherosclerotic markers. Moreover, IS induces a prothrombotic state and impaired neovascularization. IS reduction by AST-120 reverse these abnormalities. In vitro, IS induces endothelial aryl hydrocarbon receptor (AhR) activation and proinflammatory transcription factors as NF-\u03baB or AP-1. IS has a prooxidant effect with reduction of nitric oxide (NO) bioavailability. Finally, IS alters endothelial cell and endothelial progenitor cell migration, regeneration and control vascular smooth muscle cells proliferation. Reducing IS endothelial toxicity appears to be necessary to improve cardiovascular health in CKD patients.<\/jats:p>","DOI":"10.3390\/toxins12040229","type":"journal-article","created":{"date-parts":[[2020,4,9]],"date-time":"2020-04-09T14:42:03Z","timestamp":1586443323000},"page":"229","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":133,"title":["Indoxyl Sulfate, a Uremic Endotheliotoxin"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1692-5799","authenticated-orcid":false,"given":"Guillaume","family":"Lano","sequence":"first","affiliation":[{"name":"C2VN, Aix Marseille Univ, INSERM, INRAE, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1813-7884","authenticated-orcid":false,"given":"St\u00e9phane","family":"Burtey","sequence":"additional","affiliation":[{"name":"C2VN, Aix Marseille Univ, INSERM, INRAE, 13005 Marseille, France"},{"name":"Centre de N\u00e9phrologie et Transplantation R\u00e9nale, AP-HM, H\u00f4pital de la Conception, 147 Bd Baille, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Sall\u00e9e","sequence":"additional","affiliation":[{"name":"C2VN, Aix Marseille Univ, INSERM, INRAE, 13005 Marseille, France"},{"name":"Centre de N\u00e9phrologie et Transplantation R\u00e9nale, AP-HM, H\u00f4pital de la Conception, 147 Bd Baille, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1056\/NEJM199007053230106","article-title":"Regulatory functions of the vascular endothelium","volume":"323","author":"Vane","year":"1990","journal-title":"N. 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