Fig. 7.

An inhibitor of Malat1 prevented, inhibited, and reversed AngII-induced AAA in vivo. a Diagram of the experimental design for the preventive effect of the inhibitor (MALAT1-IN-1). The preventive effect of the inhibitor on AAA formation was significant with injection 2 weeks prior to AngII infusion. The results of the survival curve and the AAA incidence supported the preventive effect of the inhibitor. n = 20 per group. b The preventive effect of the inhibitor on AAA formation was revealed based on macroscopic histopathology in vivo. The maximal abdominal aortic diameter and the total aortic weights in mice injected with inhibitor were lower than those in the DMSO group. n = 20 in both D group and IN group. n = 12 in 4WA + D group and n = 15 in 4WA + IN group. c MMP2, MMP9, IL-1β, TNF-α, and tubulin protein expression in the abdominal aortas of indicated groups. n = 5 per group. d Representative staining with H&E, elastin in the abdominal aortas of indicated groups. The magnification of the two insets was 40-fold and 400-fold. e Diagram of the experimental design for the inhibitory effect of the inhibitor. The inhibitory effect of the inhibitor administered over the last 2 weeks of the 4-week continuous AngII infusion. The results of the survival curve and AAA incidence supported the inhibitory effect of the inhibitor. n = 20 per group. f The inhibitory effect of the inhibitor on AAA progression was revealed based on macroscopic histopathology in vivo. The maximal abdominal aortic diameter and the total aortic weights in mice injected with the inhibitor were lower than those in the DMSO group. n = 20 in both D group and IN group. n = 14 in 4WA + 2WD group and n = 16 in 4WA + 2WIN group. g Representative H&E and elastin staining in the abdominal aortas of indicated groups. h Diagram of the experimental design for the reversal effect of the inhibitor. The reversal effect of the inhibitor on AAA was tested by injecting it over the last 2 weeks without AngII infusion. The results of the survival curve and the AAA incidence supported the reversal effect of the inhibitor. n = 20 per group. i The reversal effect of the inhibitor on AAA was shown based on macroscopic histopathology in vivo. The maximal abdominal aortic diameter and the total aortic weights in mice injected with the inhibitor were lower than those in the DMSO group. n = 20 in both the control group and 2WA group. n = 16 in 2WA + D group and n = 18 in 2WA + IN group. j Representative H&E and elastin staining in the abdominal aortas of indicated groups. The control groups without angiotensin II were included with all results to compare the effect of the inhibitor. D, DMSO; IN, inhibitor; 4WA + D, 4-week Ang II + DMSO; 4WA + IN, 4-week Ang II + inhibitor. 4WA + 2WD, 4-week Ang II + 2-week DMSO; 4WA + 2WIN, 4-week Ang II + 2-week inhibitor. 2WA + D, 2-week Ang II + DMSO; 2WA + IN, 2-week Ang II + inhibitor. (n = 20 for each group). Data were presented as mean ± SEM and normal distributions were tested by the Shapiro–Wilk method, which showed that all data were normally distributed, except (i) (right). Log-rank test was used for the survival curve in (a, e, h). Differences in the incidence were analyzed with the chi-squared test in (a, e, h). One-way ANOVA followed by Tukey post hoc test was used for (b, f, i) (middle). Kruskal–Wallis test was used for (i) (right). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Each experiment was repeated independently for a minimum of three times