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Title
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Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome
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Author
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Abstract
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| 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-beta (TGF-beta) family of cytokines. We show that aortic aneurysm in a mouse model of MFS is associated with increased TGF-beta signaling and can be prevented by TGF-beta antagonists such as TGF-beta-neutralizing 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. |
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Language
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English
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Source (journal)
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Science / American Association for the Advancement of Science [Washington, D.C.] - Washington, D.C., 1880, currens
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Publication
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Washington, D.C.
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American Association for the Advancement of Science
,
2006
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ISSN
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0036-8075
[print]
1095-9203
[online]
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DOI
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10.1126/SCIENCE.1124287
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Volume/pages
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312
:5770
(2006)
, p. 117-121
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ISI
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000236584400045
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Full text (Publisher's DOI)
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