{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:22:38Z","timestamp":1791912158146,"version":"4.3.4"},"reference-count":87,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,10]]},"abstract":"<jats:p>\n                    Endothelial injury destroys endothelial barrier integrity, triggering organ dysfunction and ultimately resulting in sepsis-related death. Considerable attention has been focused on identifying effective targets for inhibiting damage to endothelial cells to treat endotoxemia-induced septic shock. Global gasdermin D (\n                    <jats:italic>Gsdmd<\/jats:italic>\n                    ) deletion reportedly prevents death caused by endotoxemia. However, the role of endothelial GSDMD in endothelial injury and lethality in lipopolysaccharide-induced (LPS-induced) endotoxemia and the underlying regulatory mechanisms are unknown. Here, we show that LPS increases endothelial GSDMD level in aortas and lung microvessels. We demonstrated that endothelial\n                    <jats:italic>Gsdmd<\/jats:italic>\n                    deficiency, but not myeloid cell\n                    <jats:italic>Gsdmd<\/jats:italic>\n                    deletion, protects against endothelial injury and death in mice with endotoxemia or sepsis. In vivo experiments suggested that hepatocyte GSDMD mediated the release of high-mobility group box 1, which subsequently binds to the receptor for advanced glycation end products in endothelial cells to cause systemic vascular injury, ultimately resulting in acute lung injury and lethality in shock driven by endotoxemia or sepsis. Additionally, inhibiting endothelial GSDMD activation via a polypeptide inhibitor alleviated endothelial damage and improved survival in a mouse model of endotoxemia or sepsis. These data suggest that endothelial GSDMD is a viable pharmaceutical target for treating endotoxemia and endotoxemia-induced sepsis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.182398","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T09:48:22Z","timestamp":1739353702000},"source":"Crossref","is-referenced-by-count":16,"title":["Endothelial GSDMD underlies LPS-induced systemic vascular injury and lethality"],"prefix":"10.1172","volume":"10","author":[{"given":"Enyong","family":"Su","sequence":"first","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, NHC Key Laboratory of Ischemic Heart Diseases, Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, National Clinical Research Center for Interventional Medicine, Shanghai, China."},{"name":"Shanghai Engineering Research Center of AI Technology for Cardiopulmonary Diseases, Zhongshan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyue","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, NHC Key Laboratory of Ischemic Heart Diseases, Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, National Clinical Research Center for Interventional Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, NHC Key Laboratory of Ischemic Heart Diseases, Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, National Clinical Research Center for Interventional Medicine, Shanghai, China."},{"name":"Shanghai Engineering Research Center of AI Technology for Cardiopulmonary Diseases, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Department of Cardiology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqiang","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, NHC Key Laboratory of Ischemic Heart Diseases, Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, National Clinical Research Center for Interventional Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Health Management Center, Zhongshan Hospital, and"},{"name":"Department of General Practice, Zhongshan Hospital, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyao","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, NHC Key Laboratory of Ischemic Heart Diseases, Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, National Clinical Research Center for Interventional Medicine, Shanghai, China."},{"name":"Shanghai Engineering Research Center of AI Technology for Cardiopulmonary Diseases, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Engineering Research Center of AI Technology for Cardiopulmonary Diseases, Zhongshan Hospital, Fudan University, Shanghai, China."},{"name":"Department of Health Management Center, Zhongshan Hospital, and"},{"name":"Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,2,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-021-03762-8"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1093985"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201910-1911TR"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e23599"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI170502"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(17)30268-0"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0368-3"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(85)90176-X"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-4453(95)90647-9"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.1240988"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nature10558"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nature13683"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.58"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar7607"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.11.013"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.222"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nri1594"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1320808110"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.08.016"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5425.248"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nm1124"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101323"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI94495"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nature15541"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.02.067"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.314330"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/nature15514"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-00472-6"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.172487"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00484"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-041316-085215"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.82003"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108117"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2024.5385"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.08.009"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20040831"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200418704"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-023-02332-6"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7263"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-1488-4_4"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1089\/sur.2016.021"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aat2738"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0669-6"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1800562115"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1184588"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i1585"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.15.5.726"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0069-0"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1186\/cc8048"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005043421806"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20184341"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1172\/JCI136908"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2026131"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911740"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.10.6870"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.11.010"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.06.011"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.06.017"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201308-1535OC"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.55.6.711"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00130.2004"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03520360048038"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199810000-00016"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1994.03510470040032"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1172\/JCI76887"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2022.04.003"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200319523"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2023.127383"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0054-1"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2020.109254"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/nature18629"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-021-00937-7"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.04.022"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.048"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1960"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.05.010"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.118.309669"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008942828960"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.1.305"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.121.317339"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310694"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.3791\/50062"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1186\/s12950-023-00338-x"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-019-01052-8"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-01267-z"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/182398\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:27:33Z","timestamp":1779136053000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/182398"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,10]]},"references-count":87,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2,10]]},"published-print":{"date-parts":[[2025,2,10]]}},"alternative-id":["10.1172\/jci.insight.182398"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.182398","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,10]]},"article-number":"e182398"}}