Losartan, an AT1 Antagonist, Prevents Aortic Aneurysm in a Mouse Model of Marfan Syndrome

• DOI: 10.1126/science.1124287
• Publication Date: 2006-04-06T23:22:42Z
• Authors: Jennifer P. Habashi; 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
• Keywords: Lung Diseases; Fibrillin-1; Adrenergic beta-Antagonists; Microfilament Proteins; Elastic Tissue; Fibrillins; Antibodies; Losartan; Aortic Aneurysm; Marfan Syndrome; 3. Good health; Disease Models, Animal; Mice; Neutralization Tests; Pregnancy; Mutation; Animals; Female; Angiotensin II Type 1 Receptor Blockers; Lung; Aorta

Aortic aneurysm and dissection are manifestations of Marfan syndrome (MFS), a disorder caused by mutations in the gene that encodes fibrillin-1. Selected MFS reflect excessive signaling transforming growth factor-beta (TGF-beta) family cytokines. We show aortic mouse model is associated with increased TGF-beta can be prevented antagonists such as TGF-beta-neutralizing antibody or angiotensin II type 1 receptor (AT1) blocker, losartan. AT1 antagonism also partially reversed noncardiovascular MFS, including impaired alveolar septation. These data suggest losartan, drug already clinical use for hypertension, merits investigation therapeutic strategy patients has potential to prevent major life-threatening manifestation this disorder.