Refametinib, doxycycline, and G6‐31 treatment effects in Emilin1‐deficient mice. Harts micrograph showed elastic fiber assembly defects and EFF in Emilin1‐/‐ aortic valves (arrowheads, B), and intact cusp layers, namely the fibrosa (F), spongiosa (S), and ventricularis (V) in Emilin1
+/+ valve (A), and reduction in EFF with refametinib (arrows, C) or doxycycline (arrows, E) treatment in aortic valve tissue. IHC shows p‐Erk1/2 activation in Emilin1
‐/‐ aortic valves (G) and dramatic reduction in p‐Erk1/2 expression in response to refametinib (H) or doxycycline treatment (J), and unaltered with G6‐31 (I) treatment. Western blot analysis (K) and corresponding densitometry analysis (L) show significant reduction in p‐Erk1/2 activation when treated with refametinib or doxycycline (n = 7–8/group, P < 0.0001; * different from Emilin1
+/+; # different from vehicle‐treated Emilin1
−/−). EFF, Elastic fiber fragmentation.