Activation of Wnt signaling in AAA and effect of LGK974 and PRI-724 on the formation of Ang II-induced AAA. (IMAGE)
Caption
Activation of Wnt signaling in AAA and effect of LGK974 and PRI-724 on the formation of Ang II-induced AAA. (A-B, left panels), Boxplots showing mRNA levels of WNT2, WNT5A and WNT5B (A), and their homologues in mice (B) analyzed by real-time PCR in abdominal aorta from healthy donors and patients with AAA [Donors (n = 9), AAA (n = 48); ∗P < 0.02 vs. Donors. Mann–Whitney test] or abdominal aorta from ApoE−/− mice infused with saline solution or AngII (1000 ng/kg/min for 28 days) (at least n = 9; ∗P < 0.01 vs. Saline. t-test). The box extends from the 25th to the 75th percentile, the median is indicated in horizontal line, and the whiskers represent the maximum and minimum values. (A-B, right panels), in A representative immunohistochemical analysis for active β-catenin (ABC) in abdominal aortas from AAA patients and healthy donors (black and red arrow heads indicate positive inflammatory cells and VSMC, respectively); in B representative immunoblot images showing ABC levels in abdominal aortas from animals as indicated above (levels of β-actin are shown as a loading control), and histogram showing the results (mean ± SEM) of the densitometric analysis [Saline (n = 4), AngII (n = 6); ∗P < 0.01 vs. Saline. Mann–Whitney test]. (C–F) ApoE−/− mice were infused with saline solution or AngII (1000 ng/kg/min for 28 days) and were treated or not with LGK974 (5 mg/kg/day). (C, left panel) representative images of aortas from each experimental group; (C, middle panel) data (mean ± SEM) from echocardiography analysis of the abdominal aortic diameter [Saline (n = 5), AngII (n = 14) and AngII/LGK974 (n = 8); ∗P < 0.05 vs. Saline. Two-way ANOVA]; (C, right panels) representative ultrasonographic frames after 28 days of AngII infusion. Transverse and longitudinal images taken at the level of the suprarenal aorta are shown. The aortic perimeter is indicated with a yellow line. (D) severity of AAA by experimental group (n as indicated in C middle panel). (E) Graph showing the survival rate of the experimental groups (Chi-square test). (F) Representative hematoxylin-eosin staining of abdominal aortic sections for each experimental group (bars: 200 μm). (G–J) ApoE−/− mice were infused with saline solution or AngII (1000 ng/kg/min for 28 days) and were treated or not with PRI-724 (15 mg/kg/day). (G, left panel) representative images of aortas from each experimental group; (G, middle panel) data (mean ± SEM) from echocardiography analysis of the abdominal aortic diameter [Saline (n = 5), AngII (n = 9) and AngII/PRI-724 (n = 9); ∗P < 0.05 vs. Saline. Two-way ANOVA]; (G, right panels) representative ultrasonographic frames after 28 days of AngII infusion as indicated above. D, Severity of AAA by experimental group (n as indicated in G middle panel). E, Graph showing the survival rate of the experimental groups (Chi-square test). F, Representative hematoxylin-eosin staining of abdominal aortic sections for each experimental group (bars: 200 μm).
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Genes & Diseases
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