Fig. 6: 12,13-diHOME attenuates age-induced ER stress in male mice.

a, b BAT transplantation attenuates ER stress in the hearts of aged mice; n = 5 (Young; green bar), n = 7 (aged; white bars), n = 8 (+BAT aged; blue bars). c, d TNT-Ephx1/2 reduces ER stress in the hearts of aged mice; n = 7 (sham; white bars), n = 8 (TNT; light blue bars). e Acute treatment with 12,13-diHOME (12,13-diHOME; blue bars; n = 7) attenuates ER stress compared to vehicle (9,10-diHOME; white bars; n = 7). f BAT transplantation (n = 5; blue bars) and g TNT-Ephx1/2 (n = 3; light blue bars) reduce perivascular fibrosis and wall-to-lumen ratio compared to sham controls (n = 3 or 5; white bar). Scale bar, 50 μm (black). h usXBP1/sXBP1 ratio in murine fibroblasts after incubation with tunicamycin and/or 12,13-diHOME; n = 3. Bar colors: white (PBS), blue (12,13-diHOME), red (Tunicamycin), purple (12,13-diHOME + Tunicamycin). P < 0.001 vs. PBS; ^#P < 0.001 vs. 12,13-diHOME; ^†P < 0.001 vs. Tunicamycin. i 12,13-diHOME; n = 10 (sham; white), n = 5 (TNT; red), j ejection fraction, k expression of ER stress in the heart; n = 8 or 9, and (l) PCR of usXBP1/sXBP1 ratio in the heart; TNT-Sham (n = 7; white bars) or TNT-Ephx1/2 (n = 7; gray bars) in young WT and TNT-Sham (n = 7; open red bars) or TNT-Ephx1/2 (n = 7; red bar) in nNOS−/− male mice fed a high-fat diet. P < 0.05 vs. Sham. Data are expressed as mean ± SEM (b, d, e, f, g–j, l) or mean ± SD (a, c, k). Statistical analysis was performed using two-way ANOVA with Tukey’s multiple comparisons test a, b, h or unpaired two-tailed Student’s t test (c–g, i–l). Imaging data in (f) and (g) were obtained from three independent cohorts.