Abstract 17858: Aortic Dissection and Survival in the Angiotensin II Infused ApoE Deficient Mouse- the Influence of Transforming Growth Factor Beta
The role of transforming growth factor-beta (TGFB) in the development of aortic aneurysm (AA) in the angiotensin (Ang)II infused ApoE-/- mouse is uncertain with induction of AA complicated by aortic dissection (AD) and development of atherosclerosis. We have used this model to study the short and long-term effects of inhibition of TGFB signalling on the development of AD and atherosclerosis. Twelve week old ApoE-/- mice were treated with saline (n=20), AngII (1000ng/kg/min/sc; n=20), AngII + TGFB NAB (1mg/kg/wk/ip; n=20) or AngII + losartan (30mg/kg/day/po; n=20) for 2 weeks. Ten animals from each treatment cohort were then sacrificed immediately (Grp1). A second group of animals were sacrificed 14 weeks after treatment (Grp2). At post mortem the aorta was assessed histologically for AD and graded (mean±SD) for atherosclerosis using a semiquantitative scale. Table 1 summarises the results. AD occurred at or above the renal artery with thoracic aorta involvement in about 50%. In Grp1 death due to AD occurred in up to 20% of animals in each AngII group. Histological study identified additional AD in each AngII group but these animals survived. No atherosclerosis was observed. In Grp2 death due to AD occurred in 30-40% of animals in each AngII group. On histology repaired AD with atherosclerosis (score ≥ 2.5) and adventitial hemosiderin pigment and fibrosis was also identified in 10-50% of surviving AngII treated animals. The study showed that AngII infusion induced AD with early death or survival in about 40% of animals whether or not treated with TGFB NAB or losartan (p≤0.05). In AngII +TGFB NAB or losartan groups AD survival with repair was improved and was associated with an increased atherosclerosis score compared to AngII alone (p<0.05). The results suggest that inhibition of TGFB signalling does not influence AD development but has beneficial effects on long term survival as a result of repair associated with enhanced atherosclerosis.
- © 2012 by American Heart Association, Inc.