{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T14:23:25Z","timestamp":1772893405564,"version":"3.50.1"},"reference-count":33,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Vasc Res"],"published-print":{"date-parts":[[2006]]},"abstract":"<jats:p>&lt;i&gt;Background:&lt;\/i&gt; Elevated plasma homocysteine (Hcy) is a risk factor for coronary disease. The objective of this study was to investigate whether Hcy either alone or in high glucose conditions induces endothelin-1 (ET-1) synthesis via the production of reactive oxygen species (ROS). &lt;i&gt;Methods:&lt;\/i&gt; Bovine aortic endothelial cells were grown in high (25 mmol\/l) and low (5 mmol\/l) glucose medium. &lt;i&gt;Results:&lt;\/i&gt; In high glucose, Hcy caused a time-dependent increase in ET-1 release, which was greatest with 50 \u00b5mol\/l Hcy at 24 h (p &lt; 0.01). This effect was not seen in low glucose conditions. In high glucose and 50 \u00b5mol\/l Hcy, ET-1 mRNA levels were maximal after 1 h (p &lt; 0.05). Tissue factor mRNA levels were raised at 4 h (p &lt; 0.05) and functional activity was raised at 6 h (p &lt; 0.01). Intracellular ROS production was increased by 50 \u00b5mol\/l Hcy after 24 h (p &lt; 0.05) but only in high glucose. To investigate the role of mitochondrial metabolism in ROS production, cells were incubated with thenoyltrifluoroacetone (inhibitor of complex II) or carbonyl cyanide m-chlorophenylhydrazone (uncoupler of oxidative phosphorylation). Both compounds abolished the Hcy-induced increase in ROS production and ET-1 release. There was an alteration in intracellular glutathione (GSH) levels with Hcy treatment with more oxidised GSH present. &lt;i&gt;Conclusion:&lt;\/i&gt; The combined metabolic burden of Hcy and high glucose stimulates ET-1 synthesis in bovine aortic endothelial cells via a mechanism dependent on the production of mitochondrial ROS, but may not be generalisable to all types of endothelial cells.<\/jats:p>","DOI":"10.1159\/000090947","type":"journal-article","created":{"date-parts":[[2006,1,13]],"date-time":"2006-01-13T08:39:28Z","timestamp":1137141568000},"page":"175-183","source":"Crossref","is-referenced-by-count":25,"title":["Homocysteine-Induced Endothelin-1 Release Is Dependent on Hyperglycaemia and Reactive Oxygen Species Production in Bovine Aortic Endothelial Cells"],"prefix":"10.1159","volume":"43","author":[{"given":"Amarjit S.","family":"Sethi","sequence":"first","affiliation":[]},{"given":"Delphine M.","family":"Lees","sequence":"additional","affiliation":[]},{"given":"Julie 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