Abstract 14479: Abrupt Withdrawal of Losartan Therapy Increases Circulating Transforming Growth Factor Beta and Accelerates Aortic Root Growth in a Mouse Model of Marfan Syndrome

Objective: The AT1 receptor blocker losartan has shown the ability to attenuate TGFβ signaling and aneurysm progression in a mouse model of Marfan syndrome (MFS). Losartan is known to be teratogenic and can impair renal development through birth. Therefore therapy has to be discontinued at the onset of pregnancy. AT1 blockade has been shown to upregulate receptor expression. We assessed the hypothesis that abrupt withdrawal of losartan therapy would lead to excessive AT1 activity with a consequent elevation in circulating TGFβ and aortic root growth in a mouse model of MFS. Subjects and Methods: Fbn1C1039G/+ (n=11) and wild-type mice (n=7) were randomly assigned to receive losartan therapy or placebo. Treatment in the losartan group was started at 4 months of age, continued for 2 months and then was abruptly withdrawn. Aortic root size was measured and serum samples were taken at 4, 6 and 8 months of age; serum samples were analyzed for levels of circulating TGFβ-1. Results: In keeping with prior work, fi...