{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:58:29Z","timestamp":1787507909950,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:00:00Z","timestamp":1694995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["372486779 (SFB 1340\/2)"],"award-info":[{"award-number":["372486779 (SFB 1340\/2)"]}]},{"name":"Open Access Publication Fund of Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin and the German Research Foundation (DFG)","award":["372486779 (SFB 1340\/2)"],"award-info":[{"award-number":["372486779 (SFB 1340\/2)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Uremic toxins exert pathophysiological effects on cells and tissues, such as the generation of a pro-calcifying subtype of exosome-like extracellular vesicles (EVs) in vascular cells. Little is known about the effects of the toxins on the surface structure of EVs. Thus, we studied the effects of uremic toxins on the abundance of sulfated glycosaminoglycans (GAGs) in EVs, and the implications for binding of ligands such as very small superparamagnetic iron oxide particles (VSOPs) which could be of relevance for radiological EV-imaging. Vascular cells were treated with the uremic toxins NaH2PO4 and a mixture of urea and indoxyl sulfate. Uremia in rats was induced by adenine feeding. EVs were isolated from culture supernatants and plasma of rats. By proton T1-relaxometry, magnetic particle spectroscopy, and analysis of genes, proteins, and GAG-contents, we analyzed the roles of GAGs in the ligand binding of EVs. By influencing GAG-associated genes in host cells, uremic toxins induced higher GAG contents in EVs, particularly of sulfated chondroitin sulfate and heparan sulfate chains. EVs with high GAG content interacted stronger with VSOPs compared to control ones. This was confirmed by experiments with GAG-depleted EVs from genetically modified CHO cells and with uremic rat-derived EVs. Mechanistically, uremic toxin-induced PI3K\/AKT-signaling and expression of the sulfate transporter SLC26A2 in host cells contributed to high GAG contents in EVs. In conclusion, uremic conditions induce enhanced GAG contents in EVs, which entails a stronger interaction with VSOPs. VSOPs might be suitable for radiological imaging of EVs rich in GAGs.<\/jats:p>","DOI":"10.3390\/ijms241814253","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T02:26:17Z","timestamp":1695090377000},"page":"14253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Uremic Toxin-Induced Exosome-like Extracellular Vesicles Contain Enhanced Levels of Sulfated Glycosaminoglycans which Facilitate the Interaction with Very Small Superparamagnetic Iron Oxide Particles"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2602-226X","authenticated-orcid":false,"given":"Christian","family":"Freise","sequence":"first","affiliation":[{"name":"Department of Radiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4709-5222","authenticated-orcid":false,"given":"Andreas","family":"Zappe","sequence":"additional","affiliation":[{"name":"Department of Biology, Chemistry and Pharmacy, Freie Universit\u00e4t Berlin, Altensteinstra\u00dfe 23A, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6245-9042","authenticated-orcid":false,"given":"Norbert","family":"L\u00f6wa","sequence":"additional","affiliation":[{"name":"Metrology for Magnetic Nanoparticles Berlin, Physikalisch-Technische Bundesanstalt Berlin, Abbestr. 2, 10587 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9819-3060","authenticated-orcid":false,"given":"J\u00f6rg","family":"Schnorr","sequence":"additional","affiliation":[{"name":"Department of Radiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Pagel","sequence":"additional","affiliation":[{"name":"Department of Biology, Chemistry and Pharmacy, Freie Universit\u00e4t Berlin, Altensteinstra\u00dfe 23A, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0608-1473","authenticated-orcid":false,"given":"Frank","family":"Wiekhorst","sequence":"additional","affiliation":[{"name":"Metrology for Magnetic Nanoparticles Berlin, Physikalisch-Technische Bundesanstalt Berlin, Abbestr. 2, 10587 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2994-8263","authenticated-orcid":false,"given":"Matthias","family":"Taupitz","sequence":"additional","affiliation":[{"name":"Department of Radiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Charit\u00e9platz 1, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Six, I., Flissi, N., Lenglet, G., Louvet, L., Kamel, S., Gallet, M., Massy, Z.A., and Liabeuf, S. 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