Figure 4.

Pharmacological inhibition of JMJD3 via GSK-J4 prevents AAA formation. (A) Experimental design of JMJD3 inhibition (GSK-J4) in murine AAA model. WT mice were fed a high-fat diet for 6 wk and infused with saline or AngII (1,000 ng/min/kg) for 4 wk. During this period, mice were randomized to receive either PBS or GSK-J4 (10 mg/kg) injection thrice weekly. (B) Representative ultrasound images of the abdominal aorta at day 28 in WT mice that received either saline or AngII infusion with or without GSK-J4 treatment. Dotted line represents aortic contour, and arrows represent aortic wall diameter. Scale bar represents 1-mm distance. (C and D) Maximal abdominal aortic diameter and aneurysm incidence as determined by ultrasound measured by two observers in WT mice infused with either saline or AngII with or without GSK-J4 administration (n = 6 in saline-infused cohorts and 18 in AngII-infused cohorts). *, P < 0.05; **, P < 0.001, ANOVA with Newman–Keuls multiple comparison test. Data are presented as the mean ± SEM. (E and F) Representative Masson’s trichrome staining and Verhoeff–van Gieson elastin staining of abdominal aortic sections showing preserved aortic structure in AngII + GSK-J4 mice compared with AngII + PBS mice; scale bars represent 200 µm in Masson’s trichrome and 100 µm or 50 µm in Verhoeff–van Gieson stain; arrows represent elastin fragmentation.