Fig. 1.
Postnatal treatment with TGF-β NAb. (A to H) Characterization of the ascending aorta in untreated wild-type mice [(A) and (E)] and Fbn1C1039G/+ mice treated with placebo [(B) and (F)], 1 mg/kg TGF-β NAb [(C) and (G)], and 10 mg/kg TGF-β NAb [(D) and (H)]. In (A) to (D), Verhoeff's–van Gieson (VVG) stain reveals diffuse disruption of elastic fiber architecture and thickening of the aortic media (delineated by arrows) in placebo-treated Fbn1C1039G/+ mice (B) relative to the normal elastic fiber architecture observed in wild-type mice (A). Improvement in both parameters is seen in NAb-treated Fbn1C1039G/+ mice [(C) and (D)]. Scale bars, 40 μm. In (E) to (H), immunohisto-chemistry (IH) reveals nuclear pSmad2, a marker for TGF-β signaling (arrows indicate representative positive nuclei). Increased pSmad2 is observed in the placebo-treated Fbn1C1039G/+ mice (F) relative to wild-type mice (E). Normalized pSmad2 staining is observed in the NAb-treated Fbn1C1039G/+ mice [(G) and (H)]. Scale bars, 50 μm. (I) Average aortic root growth (±SD) measured by echocardiogram over the 2-month treatment period. Note the reduced rate of growth in the NAb-treated mice relative to the placebo-treated Fbn1C1039G/+ mice. *P < 0.0001, **P < 0.03, †P = 0.11, ‡P = 1.0. (J) Average thickness (±SD) of the proximal ascending aortic media of four representative sections measured by an observer blinded to genotype and treatment arm. Note full normalization of thickness in NAb-treated Fbn1C1039G/+ mice. *P < 0.01, †P = 0.91, ‡P = 0.38. (K) Average aortic wall architecture score (±SD) of the proximal ascending aorta. Three separate observers who were blinded to genotype and treatment arm graded elastic fiber architecture in four representative areas on a scale from 1 (completely intact elastic lamellae) to 4 (extensive fragmentation). Note the improvement in NAb-treated Fbn1C1039G/+ mice. *P < 0.007, **P < 0.0001, ***P < 0.001, †P = 0.21.