MKC-3946 treatment alleviated Ang II-induced AD formation and the destruction of the middle layer of aortae in ApoE-/- mice. (A) Schematic illustration of the AD experimental mouse model. 8- week-old ApoE-/- male mice were given β-aminopropionitrile (BAPN) at a concentration of 0.1% for 3 weeks at first and infused with saline or Ang II (2500 ng/kg/min) via subcutaneous osmotic minipumps for 2 weeks. One group received MKC-3946 100 mg/kg/day intraperitoneally at the same as the Ang II osmotic minipump was implanted. (B) Representative images of aortae isolated from ApoE-/- mice in different groups. (C) H&E, α-SMA, MMP2, MMP9 immunohistochemical and elastin van Gieson staining of aortae with different interventions are shown. MKC-3946 treatment significantly alleviated Ang II induced aortic elastin degradation in the media and stabilized the aortic wall. (D) Quantitative analysis of α-SMA, MMP2 and MMP9. (E) MKC-3946 treatment significantly reduced the incidence of AD. (F-G) MKC-3946 treatment significantly decreased the AD lesion lengths and maximal abdominal aortic diameter induced by Ang II infusion. All data represent the means ± SEM; n=6 mice in saline group, n=20 mice in Ang II group, n=17 in Ang II+MKC-3946 group; * p < 0.05 vs. saline group; # p < 0.05 vs. Ang II group; One-way ANOVA.