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However, several clinical trials demonstrated that despite reduction in homocysteine levels, disease outcome remained unaffected, thus the mechanism of endothelial dysfunction is poorly defined. Here, we show that the loss of CBS function in endothelial cells (ECs) leads to a significant down\u2010regulation of cellular hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) by 50% and of glutathione (GSH) by 40%. Silencing CBS in ECs compromised phenotypic and signaling responses to the VEGF that were potentiated by decreased transcription of VEGF receptor (VEGFR)\u20102 and neuropilin (NRP)\u20101, the primary receptors regulating endothelial function. Transcriptional down\u2010regulation of VEGFR\u20102 and NRP\u20101 was mediated by a lack in stability of the transcription factor specificity protein 1 (Spl), which is a sulfhydration target of H\n                    <jats:sub>2<\/jats:sub>\n                    S at residues Cys68 and Cys755. Reinstating H\n                    <jats:sub>2<\/jats:sub>\n                    S but not GSH in CBS\u2010silenced ECs restored Sp1 levels and its binding to the VEGFR\u20102 promoter and VEGFR\u20102, NRP\u20101 expression, VEGF\u2010dependent proliferation, and migration phenotypes. Thus, our study emphasizes the importance of CBS\u2010mediated protein S\u2010sulfhydration in maintaining vascular health and function.\u2014Saha, S., Chakraborty, P. K., Xiong, X., Dwivedi, S. K. D., Mustafi, S. B., Leigh, N.R., Ramchandran, R., Mukherjee, P., Bhattacharya, R. Cystathionine \u03b2\u2010synthase regulates endothelial function\n                    <jats:italic>via<\/jats:italic>\n                    protein S\u2010sulfhydration.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    30, 441\u2010456 (2016).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.15-278648","type":"journal-article","created":{"date-parts":[[2015,9,24]],"date-time":"2015-09-24T23:38:41Z","timestamp":1443137921000},"page":"441-456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":125,"title":["Cystathionine \u03b2\u2010synthase regulates endothelial function via protein\n                    <i>S<\/i>\n                    \u2010sulfhydration"],"prefix":"10.1096","volume":"30","author":[{"given":"Sounik","family":"Saha","sequence":"first","affiliation":[{"name":"Peggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabir K.","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Peggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunhao","family":"Xiong","sequence":"additional","affiliation":[{"name":"Peggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shailendra Kumar Dhar","family":"Dwivedi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Oklahoma Health Science Center Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumyajit Banerjee","family":"Mustafi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Oklahoma Health Science Center Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah R.","family":"Leigh","sequence":"additional","affiliation":[{"name":"Developmental Vascular Biology Program and Zebrafish Drug Screening Core, Department of Obstetrics and Gynecology The Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramani","family":"Ramchandran","sequence":"additional","affiliation":[{"name":"Developmental Vascular Biology Program and Zebrafish Drug Screening Core, Department of Obstetrics and Gynecology The Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyabrata","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Peggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma USA"},{"name":"Department of Pathology University of Oklahoma Health Science Center Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Resham","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Peggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma USA"},{"name":"Department of Obstetrics and Gynecology University of Oklahoma Health Science Center Oklahoma City Oklahoma USA"},{"name":"Department of Cell Biology University of Oklahoma Health Science Center Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2004.08.037"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2005.7.813"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi010711p"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4433"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1179\/135100003125001260"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R400005200"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1999)13:5<362::AID-HUMU4>3.0.CO;2-K"},{"key":"e_1_2_7_9_1","first-page":"111","article-title":"Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis","volume":"56","author":"McCully K. 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