- Comment in:
-
Science. 2006 Apr 7;312(5770):36-7.
Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome.
Habashi JP,
Judge DP,
Holm TM,
Cohn RD,
Loeys BL,
Cooper TK,
Myers L,
Klein EC,
Liu G,
Calvi C,
Podowski M,
Neptune ER,
Halushka MK,
Bedja D,
Gabrielson K,
Rifkin DB,
Carta L,
Ramirez F,
Huso DL,
Dietz HC.
Howard Hughes Medical Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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.
PMID: 16601194 [PubMed - indexed for MEDLINE]
PMCID: PMC1482474