Objective: The effect of sexual dimorphism on aortic pathology in mouse models of Marfan Syndrome has not been defined. Therefore, we determined differences in aortic diameter expansion between sexes in fibrillin-1 hypomorphic (FBN1mgR/mgR) mice.
Methods and Results: Ascending aortic diameters from male and female FBN1mgR/mgR mice and their wild type littermates were assessed every 4 weeks from 6 to 18 weeks of age by ultrasound. Measurements were taken luminal edge to luminal edge in diastole. Differences in aortic diameters between male and female FBN1mgR/mgR mice were detected as early as 6 weeks of age (1.79 ± 0.11 vs 1.40 ± 0.12 mm; p = 0.025) while there was no significant diameter differences between sexes of wild type littermates (1.11 ± 0.12 vs 1.10 ± 0.12 mm; p = 0.94). At 18 weeks of age, differences of aortic diameters between male and female FBN1mgR/mgR mice increased further (2.61 ± 0.21 vs 1.74 ± 0.17 mm; p = 0.006), while there were no significant differences between sexes of wild type littermates (1.35 ± 0.17 vs 1.16 ± 0.17 mm; p = 0.44). External aortic diameter measured after termination at 18 weeks correlated with in vivo ultrasound measurements (R^2 = 0.955). Male FBN1mgR/mgR mice had significantly greater aortic dilation compared to their female littermates (2.45 ± 0.17 vs 1.55 ± 0.15 mm; p = 0.001). In contrast, aortic diameters were not different between sexes of wild type littermates (1.16 ± 0.13 vs 1.06 ± 0.13 mm; p = 0.56). In addition to increased aortic diameter, death due to aortic rupture by 18 weeks was more frequent in male FBN1mgR/mgR mice than in female FBN1mgR/mgR mice (50% vs 20%).
Conclusions: FBN1mgR/mgR mice exhibit sexually dimorphic ascending aortic diameters as early as 6 weeks of age. This sex difference increased with age in FBN1mgR/mgR mice, while their wild type littermates do not exhibit significant difference. Subsequent studies using this model of Marfan Syndrome should state the sex of mice.