{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:52:31Z","timestamp":1792029151375,"version":"4.4.0"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T00:00:00Z","timestamp":1678924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["RGS\\R1\\201135"],"award-info":[{"award-number":["RGS\\R1\\201135"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HLS, Aston University","award":["RGS\\R1\\201135"],"award-info":[{"award-number":["RGS\\R1\\201135"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Endothelial dysfunction is implicated in the development and aggravation of cardiovascular complications. Among the endothelium-released vasoactive factors, hydrogen sulfide (H2S) has been investigated for its beneficial effects on the vasculature through anti-inflammatory and redox-modulating regulatory mechanisms. Reduced H2S bioavailability is reported in chronic diseases such as cardiovascular disease, diabetes, atherosclerosis and preeclampsia, suggesting the value of investigating mechanisms, by which H2S acts as a vasoprotective gasotransmitter. We explored whether the protective effects of H2S were linked to the mitochondrial health of endothelial cells and the mechanisms by which H2S rescues apoptosis. Here, we demonstrate that endothelial dysfunction induced by TNF-\u03b1 increased endothelial oxidative stress and induced apoptosis via mitochondrial cytochrome c release and caspase activation over 24 h. TNF-\u03b1 also affected mitochondrial morphology and altered the mitochondrial network. Post-treatment with the slow-releasing H2S donor, GYY4137, alleviated oxidising redox state, decreased pro-caspase 3 activity, and prevented endothelial apoptosis caused by TNF-\u03b1 alone. In addition, exogenous GYY4137 enhanced S-sulfhydration of pro-caspase 3 and improved mitochondrial health in TNF-\u03b1 exposed cells. These data provide new insights into molecular mechanisms for cytoprotective effects of H2S via the mitochondrial-driven pathway.<\/jats:p>","DOI":"10.3390\/antiox12030734","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T04:10:48Z","timestamp":1679026248000},"page":"734","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["TNF-\u03b1-Mediated Endothelial Cell Apoptosis Is Rescued by Hydrogen Sulfide"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4830-9256","authenticated-orcid":false,"given":"Lorena","family":"Diaz Sanchez","sequence":"first","affiliation":[{"name":"Aston Medical School, College of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4663-5752","authenticated-orcid":false,"given":"Lissette","family":"Sanchez-Aranguren","sequence":"additional","affiliation":[{"name":"Aston Medical School, College of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Aston Medical School, College of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4054-9279","authenticated-orcid":false,"given":"Corinne M.","family":"Spickett","sequence":"additional","affiliation":[{"name":"School of Biosciences, College of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen R.","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Swansea Medical School, Swansea University, Singleton Park, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6620-8221","authenticated-orcid":false,"given":"Irundika H. K.","family":"Dias","sequence":"additional","affiliation":[{"name":"Aston Medical School, College of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kr\u00fcger-Genge, A., Blocki, A., Franke, R.P., and Jung, F. (2019). Vascular Endothelial Cell Biology: An Update. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184411"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11324","DOI":"10.3390\/ijms150711324","article-title":"Endothelial Dysfunction in Chronic Inflammatory Diseases","volume":"15","author":"Steyers","year":"2014","journal-title":"Int. J. Mol. 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