Figure 3.

Soluble epoxide hydrolase (sEH) inhibitors inhibit cardiac hypertrophy in TAC mice. (A) Mice were treated with AEPU or AUDA. Controls consisted of both TAC alone and sham-operated groups. The mice were sacrificed after 3 weeks of follow-up (scale, 1 cm). Treatment with AEPU and AUDA resulted in inhibition of the increase in TAC mouse heart size compared with controls as determined by heart/body weight ratios (mg/g). Heart/body weight ratios (mean ± SEM) were 5.7±0.4, 10.0±0.3, 5.9±0.4, and 5.4±0.3 mg/g in sham, TAC alone, TAC+AEPU, and TAC+AUDA groups, respectively (n=16; P<.05 comparing TAC alone to TAC+AEPU or TAC+AUDA). (B) Hematoxylin and eosin staining of histologic sections showing cardiac hypertrophy at 3 weeks in the TAC mouse. The images are oriented so that the atria is on top and the right ventricle is on the left (scale bars, 200 µm). (C) After 3 weeks of treatment, TAC mice showed evidence of cardiac failure with chamber dilation, while the AEPU-treated group did not. Heart condition was assessed with 2-dimensional and M-mode echocardiography. Fractional shortening (FS), a surrogate of systolic function, was calculated from left ventricle dimensions as follows: FS = ([EDD – ESD]/EDD) × 100% (FS for each group was 50.3±3.0, 23.9±3.3, 42.3±2.8, and 43.9±5.4 for sham, TAC alone, TAC+AEPU, and TAC+AUDA, respectively (n=10–16 for each group; P<.05 comparing TAC alone to TAC+AEPU or TAC+AUDA). Adapted with permission from Xu et al.³