{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:38:22Z","timestamp":1792226302375,"version":"4.4.0"},"reference-count":32,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5770","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2006,4,7]]},"abstract":"<jats:p>Aortic aneurysm and dissection are manifestations of Marfan syndrome (MFS), a disorder caused by mutations in the gene that encodes fibrillin-1. Selected manifestations of MFS reflect excessive signaling by the transforming growth factor\u2013\u03b2 (TGF-\u03b2) family of cytokines. We show that aortic aneurysm in a mouse model of MFS is associated with increased TGF-\u03b2 signaling and can be prevented by TGF-\u03b2 antagonists such as TGF-\u03b2\u2013neutralizing antibody or the angiotensin II type 1 receptor (AT1) blocker, losartan. AT1 antagonism also partially reversed noncardiovascular manifestations of MFS, including impaired alveolar septation. These data suggest that losartan, a drug already in clinical use for hypertension, merits investigation as a therapeutic strategy for patients with MFS and has the potential to prevent the major life-threatening manifestation of this disorder.<\/jats:p>","DOI":"10.1126\/science.1124287","type":"journal-article","created":{"date-parts":[[2006,4,6]],"date-time":"2006-04-06T19:22:42Z","timestamp":1144351362000},"page":"117-121","source":"Crossref","is-referenced-by-count":1586,"title":["Losartan, an AT1 Antagonist, Prevents Aortic Aneurysm in a Mouse Model of Marfan Syndrome"],"prefix":"10.1126","volume":"312","author":[{"given":"Jennifer P.","family":"Habashi","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Departments of Cell Biology and Medicine, New York University School of Medicine, New York, NY 10016, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Judge","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Departments of Cell Biology and Medicine, New York 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J. Coucke et al. Nat. Genet. in press."},{"key":"e_1_3_2_33_2","unstructured":"We thank K. Khan for expert technical assistance. Supported by the NIH (H.C.D. D.P.J. D.L.H. D.B.R. F.R.) the Smilow Center for Marfan Syndrome Research (H.C.D.) the National Marfan Foundation (H.C.D. D.P.J.) the Howard Hughes Medical Institute (H.C.D.) the Victor A. McKusick Endowment (H.C.D.) and the Dana and Albert \u201cCubby\u201d Broccoli Center for Aortic Diseases (D.P.J.). All protocols for mouse treatment were approved by the Animal Care and Use Committee of the Johns Hopkins University School of Medicine."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1124287","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T22:36:23Z","timestamp":1704839783000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1124287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,4,7]]},"references-count":32,"journal-issue":{"issue":"5770","published-print":{"date-parts":[[2006,4,7]]}},"alternative-id":["10.1126\/science.1124287"],"URL":"https:\/\/doi.org\/10.1126\/science.1124287","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1032295.372995","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,4,7]]}}}