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Many research groups have shown that hydrogen sulfide (H<jats:sub>2<\/jats:sub>S), the newest member of the gasotransmitter family, acts as a proangiogenic factor. To date, very little is known about the regulatory role of 3\u2010mercaptopyruvate sulfurtransferase (3\u2010MST), an important H<jats:sub>2<\/jats:sub>S\u2010producing enzyme in ECs. The aim of our study was to explore the potential role of 3\u2010MST in human EC bioenergetics, metabolism, and angiogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>To assess in vitro angiogenic responses, we used EA.hy926 human vascular ECs subjected to shRNA\u2010mediated 3\u2010MST attenuation and pharmacological inhibition of proliferation, migration, and tube\u2010like network formation. To evaluate bioenergetic parameters, cell respiration, glycolysis, glucose uptake, and mitochondrial\/glycolytic ATP production were measured. Finally, global metabolomic profiling was performed to determine the level of 669 metabolic compounds.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>3\u2010MST\u2010attenuated ECs subjected to shRNA or pharmacological inhibition of 3\u2010MST significantly reduced EC proliferation, migration, and tube\u2010like network formation. 3\u2010MST silencing also suppressed VEGF\u2010induced EC migration. From bioenergetic and metabolic standpoints, 3\u2010MST attenuation decreased mitochondrial respiration and mitochondrial ATP production, increased glucose uptake, and perturbed the entire EC metabolome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>3\u2010MST regulates bioenergetics and morphological angiogenic functions in human ECs. The data presented in the current report support the view that 3\u2010MST pathway may be a potential candidate for therapeutic modulation of angiogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Hydrogen Sulfide in Biology &amp; Medicine. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v177.4\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v177.4\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14574","type":"journal-article","created":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T12:43:26Z","timestamp":1547556206000},"page":"866-883","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["3\u2010Mercaptopyruvate sulfurtransferase supports endothelial cell angiogenesis and bioenergetics"],"prefix":"10.1111","volume":"177","author":[{"given":"Armita","family":"Abdollahi Govar","sequence":"first","affiliation":[{"name":"Department of Anesthesiology University of Texas Medical Branch  Galveston Texas 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