Abstract 289: Sex Hormones Influence Progression of Angiotensin II-Induced Abdominal Aortic Aneurysms in Hypercholesterolemic Mice
Objectives: Similar to humans, angiotensin II (AngII)-induced abdominal aortic aneurysms (AAA) exhibit marked sexual dimorphism with a greater prevalence in male than female mice. We demonstrated that castration of male mice reduced formation of AngII-induced AAAs, while castration of females had no effect. However, the role of sex hormones (testosterone or estrogen) on the progression of an established AAA is undefined. We tested the hypothesis that sex hormones influence the progression of AngII-induced AAAs.
Methods/Results: Male ApoE-/- male mice were infused with AngII (1,000 ng/kg/min) for 28 days to induce AAAs, stratified to sham-operated or castration groups, and subsequently infused with AngII for 56 days. Aortic lumen diameters were decreased significantly in castrated compared to sham controls (1.9 ± 0.1 vs 1.6 ± 0.1 mm, P<0.05). While external AAA diameters were not different between groups, 3D image analysis revealed increased wall/lumen ratios of AAAs from castrated compared to sham controls (9.5 ± 2.0 vs 4.8 ± 0.9 ratio; P<0.05). Increased AAA wall thickness was associated with more pronounced α-actin immunostaining and increased matrix deposition. In contrast, castration had no effect on AngII-induced atherosclerosis. LDLr-/- female mice that received a single dose of testosterone at 1 day of age to promote adult AAA susceptibility were infused with AngII. Females with an established AAA were stratified to sham-operated, castrated, and castrated+estrogen (E2, 36 μg/ml) groups for 56 days of AngII infusions. Castration of females significantly increased aortic lumen diameters compared to castrated females administered E2 (vehicle, 2.2 ±0.2; E2, 1.7 ± 0.1 mm, P<0.05). Moreover, E2 administration significantly decreased external aortic diameters (castrated, 2.6 ± 0.3; castrated+E2, 1.7 ± 0.1 mm, P<0.05). Finally, castrated females administered E2 had significantly decreased atherosclerosis compared to sham controls (38.9 ± 3.6 vs 49.6 ± 2.3 % lesion surface area; P<0.05).
Conclusions: These results indicate that testosterone contributes to AAA progression in males whereas E2 administration lowered AAA progression in female mice.
Author Disclosures: L.A. Cassis: None. Y. Wang: None. Y. Al-Siraj: None. A. Daugherty: None. S.E. Thatcher: None.
- © 2014 by American Heart Association, Inc.