Figure 5

Increased levels of TGF-β2 are detectable in plasma from 100 days old Fibulin-4^R/R mice, which reduces on Losartan treatment.

(a) TGF-β1 measurements in plasma samples showed no difference between placebo treated Fibulin-4^+/+ (n = 9), Fibulin-4^+/R (n = 8) and Fibulin-4^R/R mice (n = 10). (b) TGF-β2 was detectable in plasma of 12 out of 24 placebo treated Fibulin-4^R/R mice compared to only 2 out of 15 in placebo treated Fibulin-4^+/+ mice and 2 out of 19 in Fibulin-4^+/R mice. TGF-β2 levels are significantly higher in Fibulin-4^R/R mice compared to placebo treated Fibulin-4^+/+ and Fibulin-4^+/R mice. Losartan treatment of Fibulin-4^R/R mice seemed to reduce the TGF-β2 levels (0 out of 9) as compared to placebo treated Fibulin-4^R/R mice. The red line indicates the detection of the ELISA (Chi-square p < 0.001). (c) Kaplan-Meier survival curve shows an increased survival of Losartan treated Fibulin-4^R/Rmice compared to placebo treated Fibulin-4^R/Rmice. (d) Aortic diameter of 160 days old placebo and losartan treated Fibulin-4^+/+, Fibulin-4^+/R mice and Losartan treated Fibulin-4^R/R mice. Losartan treated Fibulin-4^R/Rmice have significantly enlarged aortic diameters compared to wild type mice, while there are no differences between placebo and Losartan Fibulin-4^+/Rmice and wild type mice. (e) HE, elastin and αSMA staining of ascending thoracic aortas. Placebo and losartan treated Fibulin-4^+/R mice (160 days old) show an increase in aortic wall thickness and some elastin breaks compared to Fibulin-4^+/+ mice. Losartan treated Fibulin-4^R/Rmice show despite of their survival disrupted aortic wall architecture. In addition, despite losartan treatment there is loss of smooth muscle cell content in the media of Fibulin-4^R/R mice. (*p < 0.05, **p < 0.01).