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Here, we show that the metabolite\n                    <jats:italic>S<\/jats:italic>\n                    -2-hydroxyglutarate (\n                    <jats:italic>S<\/jats:italic>\n                    -2HG) plays a crucial role in the regulation of endothelial quiescence. We find that\n                    <jats:italic>S<\/jats:italic>\n                    -2HG is produced in ECs after activation of the transcription factor forkhead box O1 (FOXO1), where it limits cell cycle progression, metabolic activity and vascular expansion. FOXO1 stimulates\n                    <jats:italic>S<\/jats:italic>\n                    -2HG production by inhibiting the mitochondrial enzyme 2-oxoglutarate dehydrogenase. This inhibition relies on branched-chain amino acid catabolites such as 3-methyl-2-oxovalerate, which increase in ECs with activated FOXO1. Treatment of ECs with 3-methyl-2-oxovalerate elicits\n                    <jats:italic>S<\/jats:italic>\n                    -2HG production and suppresses proliferation, causing vascular rarefaction in mice. Our findings identify a metabolic programme that promotes the acquisition of a quiescent endothelial state and highlight the role of metabolites as signalling molecules in the endothelium.\n                  <\/jats:p>","DOI":"10.1038\/s41556-021-00637-6","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T12:03:42Z","timestamp":1617278622000},"page":"413-423","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":124,"title":["Control of endothelial quiescence by FOXO-regulated metabolites"],"prefix":"10.1038","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4577-8620","authenticated-orcid":false,"given":"Jorge","family":"Andrade","sequence":"first","affiliation":[]},{"given":"Chenyue","family":"Shi","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8932-6370","authenticated-orcid":false,"given":"Ana S. 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