Abstract 5314: A Critical Role for TGF-{beta} Activity in the Protection Against Aortic Aneurysm Formation and Complications in Adult Mice

Complicated abdominal aortic aneurysm is a major cause of mortality in elderly men. Recent studies unexpectedly showed that increased angiotensin II (AII)-dependent transforming growth factor (TGF)-β activity promotes aortic aneurysm progression in a mouse model of Marfan syndrome. However, the direct role of TGF-β activity in other forms of abdominal aortic aneurysm has not been assessed. Here, we show that systemic neutralization of TGF-β activity using two different antibodies, including the one previously shown to inhibit aneurysm formation in Marfan syndrome, breaks the resistance of normo-cholesterolemic C57BL/6 mice to AII-induced abdominal aortic aneurysm formation and markedly increases their susceptibility to the disease (from ~ 10% to 80–95%, P<0.0001). These aneurysms display a large spectrum of complications on echography, including fissuration, false channel formation and rupture, leading to death from aneurysm complications. The disease and its complications are refractory to inhibition of ...