{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:57:12Z","timestamp":1789390632730,"version":"build-2803163510"},"reference-count":43,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["HL123301"],"award-info":[{"award-number":["HL123301"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["HL07736-17"],"award-info":[{"award-number":["HL07736-17"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007179","name":"University of New Mexico (UNM)","doi-asserted-by":"publisher","award":["3U0023"],"award-info":[{"award-number":["3U0023"]}],"id":[{"id":"10.13039\/100007179","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2017,4,1]]},"abstract":"<jats:p> Sleep apnea is a risk factor for cardiovascular disease, and intermittent hypoxia (IH, 20 episodes\/h of 5% O<jats:sub>2<\/jats:sub>-5% CO<jats:sub>2<\/jats:sub> for 7 h\/day) to mimic sleep apnea increases blood pressure and impairs hydrogen sulfide (H<jats:sub>2<\/jats:sub>S)-induced vasodilation in rats. The enzyme that produces H<jats:sub>2<\/jats:sub>S, cystathionine \u03b3-lyase (CSE), is decreased in rat mesenteric artery endothelial cells (EC) following in vivo IH exposure. In silico analysis identified putative nuclear factor of activated T cell (NFAT) binding sites in the CSE promoter. Therefore, we hypothesized that IH exposure reduces Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]) activation of calcineurin\/NFAT to lower CSE expression and impair vasodilation. In cultured rat aortic EC, inhibiting calcineurin with cyclosporine A reduced CSE mRNA, CSE protein, and luciferase activity driven by a full-length but not a truncated CSE promoter. In male rats exposed to sham or IH conditions for 2 wk, [Ca<jats:sup>2+<\/jats:sup>] in EC in small mesenteric arteries from IH rats was lower than in EC from sham rat arteries (\u0394fura 2 ratio of fluorescence at 340 to 380 nm from Ca<jats:sup>2+<\/jats:sup> free: IH = 0.05 \u00b1 0.02, sham = 0.17 \u00b1 0.03, P &lt; 0.05), and fewer EC were NFATc3 nuclear positive in IH rat arteries than in sham rat arteries (IH = 13 \u00b1 3, sham = 59 \u00b1 11%, P &lt; 0.05). H<jats:sub>2<\/jats:sub>S production was also lower in mesenteric tissue from IH rats vs. sham rats. Endothelium-dependent vasodilation to acetylcholine (ACh) was lower in mesenteric arteries from IH rats than in arteries from sham rats, and inhibiting CSE with \u03b2-cyanoalanine diminished ACh-induced vasodilation in arteries from sham but not IH rats but did not affect dilation to the H<jats:sub>2<\/jats:sub>S donor NaHS. Thus, IH lowers EC [Ca<jats:sup>2+<\/jats:sup>], NFAT activity, CSE expression and activity, and H<jats:sub>2<\/jats:sub>S production while inhibiting NFAT activation lowers CSE expression. The observations that IH exposure decreases NFATc3 activation and CSE-dependent vasodilation support a role for NFAT in regulating endothelial H<jats:sub>2<\/jats:sub>S production. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY This study identifies the calcium-regulated transcription factor nuclear factor of activated T cells as a novel regulator of cystathionine \u03b3-lyase (CSE). This pathway is basally active in mesenteric artery endothelial cells, but, after exposure to intermittent hypoxia to mimic sleep apnea, nuclear factor of activated T cells c3 nuclear translocation and CSE expression are decreased, concomitant with decreased CSE-dependent vasodilation. <\/jats:p>","DOI":"10.1152\/ajpheart.00952.2015","type":"journal-article","created":{"date-parts":[[2017,1,27]],"date-time":"2017-01-27T22:10:19Z","timestamp":1485555019000},"page":"H791-H799","source":"Crossref","is-referenced-by-count":19,"title":["NFAT regulation of cystathionine \u03b3-lyase expression in endothelial cells is impaired in rats exposed to intermittent hypoxia"],"prefix":"10.1152","volume":"312","author":[{"given":"Laura V.","family":"Gonzalez Bosc","sequence":"first","affiliation":[{"name":"Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Osmond","sequence":"additional","affiliation":[{"name":"Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wieslawa K.","family":"Giermakowska","sequence":"additional","affiliation":[{"name":"Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn E.","family":"Pace","sequence":"additional","affiliation":[{"name":"Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Riggs","sequence":"additional","affiliation":[{"name":"Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olan","family":"Jackson-Weaver","sequence":"additional","affiliation":[{"name":"Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Kanagy","sequence":"additional","affiliation":[{"name":"Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfr560"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/NRL.0b013e3181f097cb"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2174\/187152510792481207"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00405.2010"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.296"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-010-0804-6"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705756"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00341.2010"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00132.2008"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702679200"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1983.tb08809.x"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1159\/000159220"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.10.084"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312920200"},{"key":"B15","first-page":"1","volume":"7","author":"Gryglewski RJ","year":"2001","journal-title":"Med Sci Monit"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-1738(02)00212-8"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6878"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001381200"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040243"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00506.2012"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.228999"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1089\/met.2012.0045"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.37.2.511"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00134.2015"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307004"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2014.03.008"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00576.2009"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.963314"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.15.1.707"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2010.02.010"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01065-10"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1042\/bj2060267"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1006\/mvre.2000.2291"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000081980.63146.69"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.17.2230"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.5152\/akd.2010.044"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.001631"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2007.02.029"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24006"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1126\/science.1162667"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/428473"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.21.6008"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00952.2015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T01:46:24Z","timestamp":1567993584000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00952.2015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,1]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2017,4,1]]}},"alternative-id":["10.1152\/ajpheart.00952.2015"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00952.2015","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,1]]}}}