Circulating TGF in Marfan's Syndrome

Background—Marfan syndrome (MFS) is caused by mutations in the fibrillin-1 gene and dysregulation of transforming growth factor �� (TGF��). Recent evidence suggests that losartan, an AT1 blocker that blunts TGF�� activation, may be an effective treatment for MFS. We hypothesized that dysregulation of TGF�� might be mirrored in circulating TGF�� concentrations. Methods and Results—Serum obtained from MFS mutant mice (Fbn1 C1039G/+ ) treated with losartan was analyzed for circulating TGF��1 concentrations, and compared to those from placebo treated and wild-type mice. Aortic root size was measured by echocardiography. Data was validated in patients with MFS and healthy individuals. In mice, circulating total TGF��1 concentrations increased with age and were elevated in older untreated Fbn1 C1039G/+ mice compared to wild-type