Therapeutic effects in the aorta. (A) WT (n = 5), AT2KO (n = 4), Fbn1C1039G/+ (n = 7), and AT2KO:Fbn1C1039G/+ (n = 7) mice. Verhoeff–Van Gieson (VVG) stain reveals diffuse fragmentation of elastic fibers and thickening of the media in Fbn1C1039G/+ mice; these findings are exaggerated in AT2KO:Fbn1C1039G/+ mice. (B) Average aortic root growth (T2SEM) over 7 months of treatment in placebo- (n = 13) orlosartan- (n = 7) treated WT mice and placebo- (n = 17), losartan- (n = 5), or enalapril- (n = 15) treated Fbn1C1039G/+ mice, as measured by echocardiography. Note the regression in aortic size observed in losartan-treated Fbn1C1039G/+ mice and the marginal (P = 0.05) decrease in growth in the enalapril-treated cohort. Final absolute aortic root diameter: WT (1.74 ± 0.10 mm), losartan-treated WT (1.77 ± 0.15 mm), Fbn1C1039G/+ (2.19 ± 0.19 mm), losartan-treated Fbn1C1039G/+ (1.96 ± 0.09 mm), and enalapril-treated Fbn1C1039G/+ (2.18 ± 0.18 mm). (C) Average aortic root growth (±2SEM) over 7 months of treatment in WT (n = 8), placebo- (n = 22), and losartan- (n = 11) treated Fbn1C1039G/+ mice and placebo- (n = 19) and losartan- (n = 6) treated AT2KO:Fbn1C1039G/+ mice. Note the diminished effectiveness of losartan treatment in AT2KO:Fbn1C1039G/+ mice, as compared with losartan treatment in Fbn1C1039G/+ mice. Final absolute aortic root diameter: WT (1.77 ± 0.10 mm), Fbn1C1039G/+ (2.13 ± 0.16 mm), AT2KO:Fbn1C1039G/+ (2.34 ± 0.13 mm), losartan-treated Fbn1C1039G/+ (1.96 ± 0.09 mm), and losartan-treated AT2KO:Fbn1C1039G/+ (2.06 ± 0.07 mm). *P < 0.05; **P < 0.01; †P < 0.001; ††P < 0.0001; NS, not significant.