Fig. 7: MMP12 drives AAA development triggered by lung damage.

MitoSOX quantification of WT and Ripk3^−/− BMDM treated with HMGB1 (a) and WT BMDM treated with HMGB1 in the presence or not of Mdivi-1 or MitoTEMPO (b). n = 3. *P < 0.05, ***P < 0.001. (c) Relative mRNA expression of Glud1 in WT or Ripk3^−/− BMDM. n = 3 per group. *P < 0.05, ***P < 0.001. (d) Representative IF images of dihydroethidium (DHE) staining (red) of aortic sections of mice treated as indicated. Elastin autofluorescence (green, scale bar = 20 µm). (e) Heatmap representation of differentially expressed genes in macrophages expressing Ripk3 (Ripk3⁺) or not (Ripk3⁻). (f) qPCR analysis of Mmp12 mRNA in WT or Ripk3^−/− aortas. n = 3 per group. **P < 0.01, ***P < 0.001. (g) Spider graph representation (Log₁₀ scale) of multiplex analysis of MMPs in aortic extracts from WT or Ripk3^−/− mice. n = 3 (Ripk3^−/−) and 4 (WT). *P = 0.0454. Representative image of IF staining of MMP12, and its colocalization with CD68 macrophages in aortic section of mice treated as indicated (h, i). Scale bar = 20 µm. (j) Mmp12 mRNA in WT or Ripk3^−/− BMDM treated with HMGB1 (10 ng ml⁻¹) in the presence or not of Mdivi-1 (10 µM) or MitoTEMPO (10 µM). n = 3 per group. *P < 0.05, **P < 0.01. (k) Schematic representation of experimental protocol (top) and incidence of AAA in WT and Mmp12^−/− mice (below). i.n. intranasal. n = 4–5 per group. Representative color Doppler ultrasound images of aorta and M-mode screenshots (arrow) (i). Chronological quantifications of aortic diameter (m), maximal aortic diameter (n), and representative Verhoeff-Van Gieson staining in aortic sections of WT and Mmp12^−/− mice in the presence of ALI (o). n = 3 per group. Arrows indicate elastin breaks. Data is presented as mean, error bars represent s.e.m. (scale bar = 50 µm). *P = 0.0364. P va/clues were calculated by one-tailed (g) or two-tailed (m, n) unpaired t-tests, or one-way ANOVA (a–f, j).