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. 2017 Jan 5;120(1):49–65. doi: 10.1161/CIRCRESAHA.116.309321

Figure 8.

Figure 8.

Inhibition of microRNA (miR)-181b attenuates mortality rates in Timp3−/−/Apoe−/− mice by directly stimulating elastin expression in vascular smooth muscle cells (VSMCs) and abdominal aortic aneurysms (AAAs). A, Kaplan–Meier curves of survival free from aneurysm rupture in control and miR-181b inhibitor-treated Ang II–infused hypercholesterolemic Timp3−/− Apoe−/− mice, n=10 to 20/group. B, Quantification and associated representative images of aneurysm severity in control and miR-181b inhibitor-treated Timp3−/− Apoe−/− mice, n=6 to 7/group. Quantification of (C) vessel diameter, (D) collagen content, (E) elastin breaks, (F) elastin content, and (G) representative images of elastin van Gieson–stained AAAs from control and miR-181b inhibitor-treated Timp3−/− Apoe−/− mice, n=6 to 7/group, scale bar in i represents 200 μm and is applicable to panels i and ii, scale bar in ii represents 100 μm and is applicable to panels iii and iv. H, Conserved miR-181b–binding sites of the 3′-untranslated region (3′-UTR) of human (hsa) and murine (mmu) elastin (ELN). PCT refers to the probability of preferentially conserved targeting, demonstrating miR-181b preferentially targets ELN in both species. I, 3′-UTR luciferase reporter activity of human ELN in HeLa cells treated with an miR-181b inhibitor or a scrambled control, n=6. J, Representative Western blot and quantification of elastin protein expression in human aortic smooth muscle cells after addition of an miR-181b inhibitor or a scrambled control, n=4. Statistical comparisons were made using log-rank test (A), Fisher exact test (B), or 2-tailed Student t test (C–J), *P<0.05, **P<0.01, and **P<0.01 compared with controls. In all cases, data represent the mean±SEM.