{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:06:47Z","timestamp":1785424007181,"version":"3.56.0"},"reference-count":39,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund (Qatar Research, Development and Innovation Council","doi-asserted-by":"publisher","award":["NPRP14S-0406-210150"],"award-info":[{"award-number":["NPRP14S-0406-210150"]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund (Qatar Research, Development and Innovation Council","doi-asserted-by":"publisher","award":["GSRA10-L-1-0612-23121"],"award-info":[{"award-number":["GSRA10-L-1-0612-23121"]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"publisher"}]},{"award":["NPRP14S-0406-210150"],"award-info":[{"award-number":["NPRP14S-0406-210150"]}],"id":[{"id":"https:\/\/ror.org\/01svaqq28","id-type":"ROR","asserted-by":"publisher"}]},{"award":["GSRA10-L-1-0612-23121"],"award-info":[{"award-number":["GSRA10-L-1-0612-23121"]}],"id":[{"id":"https:\/\/ror.org\/01svaqq28","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004252","name":"Qatar University","doi-asserted-by":"publisher","award":["QUST-1-CPH-2025-246"],"award-info":[{"award-number":["QUST-1-CPH-2025-246"]}],"id":[{"id":"10.13039\/501100004252","id-type":"DOI","asserted-by":"publisher"}]},{"award":["QUST-1-CPH-2025-246"],"award-info":[{"award-number":["QUST-1-CPH-2025-246"]}],"id":[{"id":"https:\/\/ror.org\/00yhnba62","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic hyperglycemia and excessive reactive oxygen species (ROS) production are defining features of endothelial dysfunction, a key driver of diabetic vascular complications such as diabetic nephropathy. Microvesicles (MV-enriched fraction), a subtype of extracellular vesicles, and the stress-responsive antioxidant protein Sestrin2 (SESN2) have emerged as important contributors to these processes. This study investigated the role of the MV-enriched fraction in endothelial cell communication under diabetic conditions, with a particular focus on oxidative stress signaling. To model diabetic injury, EA.hy926 endothelial cells were treated with methylglyoxal (MGO), and the resulting MV-enriched fraction was isolated and then applied to two recipient models: na\u00efve endothelial cells and SESN2 knockdown (KD) cells. Protein expression of key antioxidant markers, including endothelial nitric oxide synthase (eNOS), was assessed by Western blot. Nitric oxide (NO) bioavailability was quantified via nitrite measurement using 2,3-diaminonaphthalene (DAN), while mitochondrial and cytosolic ROS levels were evaluated using MitoSOX and dihydroethidium (DHE), respectively. Results demonstrated that the MV-enriched fraction derived from diabetic conditions triggers a complex antioxidant response in healthy endothelial cells, characterized by upregulation of SESN2, superoxide dismutase 1 (SOD1), and heme oxygenase-1 (HO-1). This suggests a compensatory mechanism that mitigates oxidative stress. Notably, SESN2 KD cells exhibited increased ROS production and reduced NO levels upon MV treatment, underscoring the essential role of SESN2 in maintaining redox homeostasis. Overall, this study highlights the dual role of the MV-enriched fraction as a mediator of both protective and detrimental redox signaling in diabetic endothelial dysfunction and suggests potential therapeutic targets for managing diabetic vascular complications.<\/jats:p>","DOI":"10.3390\/ijms27136005","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:43:14Z","timestamp":1783345394000},"page":"6005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microvesicle-Derived Redox Signatures as Mediators of Endothelial Dysfunction in Diabetes"],"prefix":"10.3390","volume":"27","author":[{"given":"Sarah Khalaf","family":"Ghanem","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha P.O. 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Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8363-1582","authenticated-orcid":false,"given":"Abdelali","family":"Agouni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,4]]},"reference":[{"key":"ref_1","unstructured":"Magliano, D.J., Boyko, E.J., and IDF Diabetes Atlas 10th edition scientific committee (2021). IDF Diabetes Atlas, International Diabetes Federation. [10th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Caturano, A., Rocco, M., Tagliaferri, G., Piacevole, A., Nilo, D., Di Lorenzo, G., Iadicicco, I., Donnarumma, M., Galiero, R., and Acierno, C. (2025). 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