Fig. 1.

Canonical and noncanonical TGFβ signaling in the proximal ascending aorta. (A) Western blot analysis of 4 WT and Fbn1^C1039G/+ mice. Note that only pSmad2, pERK1/2, and pMEK1 signaling are increased in Fbn1^C1039G/+ mice. The graphs show normalization to β-actin, but the same outcomes were observed with normalization to the respective total proteins. (B) Western blot analysis of three each of WT and of Fbn1^C1039G/+ mice treated with placebo, TGFβNAb, or losartan. Note the significant reduction in pERK1/2 signaling after treatment with TGFβNAb (NAb) or losartan (Los). (C) Aortic root growth in placebo-treated WT (n = 5), placebo-treated Fbn1^C1039G/+ (n = 6), RDEA119-treated WT (n = 3), and RDEA119-treated Fbn1^C1039G/+ (n = 7) mice. Note that RDEA119 therapy selectively reduced growth in Fbn1^C1039G/+ mice. Final absolute aortic root diameter (mm): WT (1.62 ± 0.08), placebo-treated Fbn1^C1039G/+ (2.15 ± 0.17), RDEA119-treated WT (1.64 ± 0.09), RDEA119-treated Fbn1^C1039G/+ (1.94 ± 0.07). (D) Western blot analysis of three placebo- and three RDEA119-treated Fbn1^C1039G/+ mice, showing a selective reduction in pERK1/2 signaling in RDEA119-treated mice. Plac, placebo. Values are means ± 2SEM. *P < 0.05; **P < 0.01; †P < 0.001; NS, not significant.