{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:06:21Z","timestamp":1791047181908,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":46,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82370262,82500498"],"award-info":[{"award-number":["82370262,82500498"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"crossref","award":["BK20250767"],"award-info":[{"award-number":["BK20250767"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82570476"],"award-info":[{"award-number":["82570476"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,8]]},"abstract":"<jats:p>\n                    Aortic dissection (AD) is a catastrophic vascular emergency with high mortality, and current pharmacological interventions to prevent its progression are limited. Vascular smooth muscle cells (VSMCs) undergo a pathological phenotypic switch from a contractile to a synthetic state during AD, compromising aortic wall integrity; however, the underlying metabolic mechanisms remain poorly understood. In this study, we performed integrative transcriptomic analyses and identified glutaminase 1 (GLS1) as a key regulator of VSMC phenotypic switching in AD. GLS1 expression was significantly downregulated in VSMCs from both human AD aortic tissues and mouse models. Functionally, GLS1 deficiency promoted PDGF-BB\u2013induced VSMC dedifferentiation in vitro. Smooth muscle cell\u2013specific\n                    <jats:italic>Gls1<\/jats:italic>\n                    -knockout (\n                    <jats:italic>\n                      Gls1\n                      <jats:sup>SMKO<\/jats:sup>\n                    <\/jats:italic>\n                    ) mice exhibited aggravated AD after \u03b2-aminopropionitrile treatment, whereas VSMC-specific GLS1 overexpression improved the contractile phenotype and reduced AD incidence. Mechanistically, GLS1 downregulation impaired glutamate metabolism, leading to reduced levels of glutathione and \u03b1-ketoglutarate. This metabolic disruption promoted reactive oxygen species accumulation and mitochondrial dysfunction, ultimately triggering VSMC phenotypic switching. Furthermore, we found that\n                    <jats:italic>GLS1<\/jats:italic>\n                    transcription was repressed by retinoic acid receptor-\u03b1 (RAR\u03b1). Pharmacological inhibition of RAR\u03b1 with AR7 restored GLS1 expression, ameliorated VSMC phenotypic switching, and conferred protection against AD. These findings reveal a critical role of GLS1-mediated glutamate metabolism in VSMC phenotypic switching and suggest a promising therapeutic strategy for AD.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.203575","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T16:00:47Z","timestamp":1776960047000},"source":"Crossref","is-referenced-by-count":1,"title":["GLS1 governs vascular smooth muscle cell phenotypic switching and aortic dissection via glutamate metabolism"],"prefix":"10.1172","volume":"11","author":[{"given":"Wei","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Ning","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Song","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.53"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.534198"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00003.2017"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-024-01053-1"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/eci.13697"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.057623"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa352"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab605"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.124.325049"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2010.05.003"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-08-0107"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202401251R"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.057879"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1011"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2024.1365447"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2012.11.022"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.31200"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.03.016"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi5192"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2428-0"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12020434"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.71"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119365"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.826861"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.34888"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.advms.2024.09.006"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2023.117430"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103302"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0810199105"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11321"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac907"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404572"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.04.043"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2013.10.027"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.313366"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1621425114"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2018.02.010"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.4c10955"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107260"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.7150\/thno.70692"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1059"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.123.322654"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/203575\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T18:25:26Z","timestamp":1782757526000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/203575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,4,23]]},"published-print":{"date-parts":[[2026,6,8]]}},"alternative-id":["10.1172\/jci.insight.203575"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.203575","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]},"article-number":"e203575"}}