Title
|
|
|
|
Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome
| |
Author
|
|
|
|
| |
Abstract
|
|
|
|
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. |
| |
Language
|
|
|
|
English
| |
Source (journal)
|
|
|
|
Science / American Association for the Advancement of Science [Washington, D.C.] - Washington, D.C., 1880, currens
| |
Publication
|
|
|
|
Washington, D.C.
:
American Association for the Advancement of Science
,
2006
| |
ISSN
|
|
|
|
0036-8075
[print]
1095-9203
[online]
| |
DOI
|
|
|
|
10.1126/SCIENCE.1124287
| |
Volume/pages
|
|
|
|
312
:5770
(2006)
, p. 117-121
| |
ISI
|
|
|
|
000236584400045
| |
Full text (Publisher's DOI)
|
|
|
|
| |
|