{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T22:15:03Z","timestamp":1791756903272,"version":"4.3.4"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"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":[[2022,2,8]]},"abstract":"<jats:p>\n                    Aortic dissection and rupture are triggered by decreased vascular wall strength and\/or increased mechanical loads. We investigated the role of mTOR signaling in aortopathy using a well-described model of angiotensin II\u2013induced dissection, aneurysm, or rupture of the suprarenal abdominal aorta in\n                    <jats:italic>Apoe<\/jats:italic>\n                    -deficient mice. Although not widely appreciated, nonlethal hemorrhagic lesions present as pseudoaneurysms without significant dissection in this model. Angiotensin II\u2013induced aortic tears result in free rupture, contained rupture with subadventitial hematoma (forming pseudoaneurysms), dilatation, or healing, while the media invariably thickens regardless of mural tears. Medial thickening results from smooth muscle cell hypertrophy and extracellular matrix accumulation, including matricellular proteins. Angiotensin II activates mTOR signaling in vascular wall cells, and inhibition of mTOR signaling by rapamycin prevents aortic rupture but promotes dissection. Decreased aortic rupture correlates with decreased inflammation and metalloproteinase expression, whereas extensive dissection correlates with induction of matricellular proteins that modulate adhesion of vascular cells. Thus, mTOR activation in vascular wall cells determines whether aortic tears progress to dissection or rupture. Previous mechanistic studies of aortic aneurysm and dissection by angiotensin II in\n                    <jats:italic>Apoe<\/jats:italic>\n                    -deficient mice should be reinterpreted as clinically relevant to pseudoaneurysms, and mTOR inhibition for aortic disease should be explored with caution.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.155815","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T14:00:56Z","timestamp":1644242456000},"source":"Crossref","is-referenced-by-count":28,"title":["mTOR inhibition prevents angiotensin II\u2013induced aortic rupture and pseudoaneurysm but promotes dissection in Apoe-deficient mice"],"prefix":"10.1172","volume":"7","author":[{"given":"Changshun","family":"He","sequence":"first","affiliation":[{"name":"Department of Surgery (Cardiac), Yale School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Jiang","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"}]},{"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"}]},{"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":"Alexander W.","family":"Caulk","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":"Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, Connecticut, USA."},{"name":"Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos J.","family":"Lovoulos","sequence":"additional","affiliation":[{"name":"Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA."},{"name":"Department of Surgery, Frank H. 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