Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome

  • Science. 2006 Apr 7;312(5770):117-21. doi: 10.1126/science.1124287.
Jennifer P Habashi  1 ,  Daniel P Judge ,  Tammy M Holm ,  Ronald D Cohn ,  Bart L Loeys ,  Timothy K Cooper ,  Loretha Myers ,  Erin C Klein ,  Guosheng Liu ,  Carla Calvi ,  Megan Podowski ,  Enid R Neptune ,  Marc K Halushka ,  Djahida Bedja ,  Kathleen Gabrielson ,  Daniel B Rifkin ,  Luca Carta ,  Francesco Ramirez ,  David L Huso ,  Harry C Dietz
Affiliations
  • 1. Howard Hughes Medical Institute and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
PMID: 16601194 DOI: 10.1126/science.1124287
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.

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