{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:30:40Z","timestamp":1789036240304,"version":"build-2803163510"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":41,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01 HL152187"],"award-info":[{"award-number":["R01 HL152187"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01 HL152197"],"award-info":[{"award-number":["R01 HL152197"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["P01 HL169168"],"award-info":[{"award-number":["P01 HL169168"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"crossref","award":["erAADicate Network"],"award-info":[{"award-number":["erAADicate Network"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["R01 HL146723"],"award-info":[{"award-number":["R01 HL146723"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,24]]},"abstract":"<jats:p>Hypertension and transient increases in blood pressure from extreme exertion are risk factors for aortic dissection in patients with age-related vascular degeneration or inherited connective tissue disorders. Yet, a common experimental model of angiotensin II\u2013induced aortopathy in mice appears independent of high blood pressure, as lesions do not occur in response to an alternative vasoconstrictor, norepinephrine, and are not prevented by cotreatment with a vasodilator, hydralazine. We investigated vasoconstrictor administration to adult mice following 1 week of disrupted TGF-\u03b2 signaling in smooth muscle cells (SMCs). Norepinephrine increased blood pressure and induced aortic dissection by 7 days and even within 30 minutes (as did angiotensin II) that was prevented by hydralazine. Initial medial injury manifested as blood extravasation among SMCs and fibrillar matrix, progressive delamination from accumulation of blood, and stretched or ruptured SMCs with persistent attachments to elastic fibers. Altered regulatory contractile molecule expression was not of pathological importance. Rather, reduced synthesis of extracellular matrix yielded a vulnerable aortic phenotype by decreasing medial collagen, most dynamically basement membrane\u2013associated multiplexin collagen, and impairing cell-matrix adhesion. We conclude that transient and sustained increases in blood pressure can cause dissection in aortas rendered vulnerable by inhibition of TGF-\u03b2\u2013driven extracellular matrix production by SMCs.<\/jats:p>","DOI":"10.1172\/jci.insight.182629","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T12:00:38Z","timestamp":1739275238000},"source":"Crossref","is-referenced-by-count":10,"title":["Short-term disruption of TGF-\u03b2 signaling in adult mice renders the aorta vulnerable to hypertension-induced dissection"],"prefix":"10.1172","volume":"10","author":[{"given":"Bo","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Surgery (Cardiac), Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengwei","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Surgery (Cardiac), Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changshun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Surgery (Cardiac), Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery (Cardiac), Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6578-4585","authenticated-orcid":true,"given":"Sae-Il","family":"Murtada","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale School of Engineering and Applied Science, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jes\u00fas","family":"Ruiz-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Surgery (Cardiac), Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery (Cardiac), Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay B.","family":"Ramachandra","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale School of Engineering and Applied Science, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Surgery (Cardiac), Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingfeng","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Surgery (Cardiac), Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0863-9867","authenticated-orcid":true,"given":"Roland","family":"Assi","sequence":"additional","affiliation":[{"name":"Department of Surgery (Cardiac), Yale School of Medicine, New Haven, Connecticut, USA."},{"name":"Program in Vascular Biology and Therapeutics, Yale School of Medicine, New Haven, Connecticut, USA."},{"name":"Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2071-1243","authenticated-orcid":true,"given":"Martin A.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale School of Engineering and Applied Science, New Haven, Connecticut, USA."},{"name":"Department of Medicine (Cardiology),"},{"name":"Department of Cell Biology, and"},{"name":"Yale Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1011-2025","authenticated-orcid":true,"given":"Jay D.","family":"Humphrey","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Yale School of Engineering and Applied Science, New Haven, Connecticut, USA."},{"name":"Program in Vascular Biology and Therapeutics, Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7042-8190","authenticated-orcid":true,"given":"George","family":"Tellides","sequence":"additional","affiliation":[{"name":"Department of Surgery (Cardiac), Yale School of Medicine, New Haven, Connecticut, USA."},{"name":"Program in Vascular Biology and Therapeutics, Yale School of Medicine, New Haven, Connecticut, USA."},{"name":"Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1136\/heart.85.4.365"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2012.11.067"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2020.05.029"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7818"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00028.2009"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.05.014"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00521.2014"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/ng1511"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.0259"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.013169"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69942"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.306573"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.02.013"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI61498"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/srep35444"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nm1666"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20335"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.283"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2010.00009"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.26.4.650"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1115\/1.1824130"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1242\/dev.151142"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.307436"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmbbm.2020.104264"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.140558"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-10-298"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38308"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38136"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2017.0327"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2007.04.015"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069167"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00466.2003"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0048462"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/aap.12035"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2021.0336"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.302157"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.155815"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.826495"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.12945\/j.aorta.2017.17.003"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.312436"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/genes12020183"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.5.1852"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.653980"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2017.06.006"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.127748"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-017-9753-1"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.309401"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.121.315878"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1115\/1.4042171"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb14931.x"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1161\/hc4501.099729"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a004978"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/S0344-0338(86)80151-0"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/BF00217851"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199910)181:1<153::AID-JCP16>3.0.CO;2-K"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.122.317603"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1172\/JCI131048"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1009683"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.1.451"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06519-0"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0441-z"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1186\/s40885-016-0052-y"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008273"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.23054"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/182629\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:20:48Z","timestamp":1779135648000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/182629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,11]]},"references-count":64,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,2,4]]},"published-print":{"date-parts":[[2025,3,24]]}},"alternative-id":["10.1172\/jci.insight.182629"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.182629","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.04.22.590484","asserted-by":"object"}]},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,11]]},"article-number":"e182629"}}