Potential Cardioprotective Effects and Lipid Mediator Differences in Long-Chain Omega-3 Polyunsaturated Fatty Acid Supplemented Mice Given Chemotherapy

Figures

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  Figure 1. (A) Body weight and (B) heart weight between groups. Data presented as group means ± SEM (n = 9/group). Two-way ANOVA was used to detect differences between groups. #—p < 0.05 difference between vehicle and chemo mice. Chemo—9 mg/kg anthracycline + 90 mg/kg cyclophosphamide injections; ♀-OVX—female ovariectomy; Veh—saline vehicle injections; Low n-3—0 g/kg EPA + DHA diet; High n-3—12.2 g/kg EPA + DHA diet (~2% kcal).

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  Figure 2. Heart gene expression of (A) Myh6, (B) Myh7, and (C) Col3a1. Data presented as group means ± SEM (n = 5/group). A two-way ANOVA with a diet x chemo interaction was used to detect the differences between factors. Pairwise comparisons for variables with significant interactions were performed using a Tukey’s post hoc test. Variables with different annotations were different at p < 0.05. Veh—saline vehicle injections; Chemo—9 mg/kg anthracycline + 90 mg/kg cyclophosphamide injections; Low n-3—0 g/kg EPA + DHA diet; High n-3—12.2 g/kg EPA + DHA diet (~2% kcal).

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  Figure 3. Heart mitochondrial lipid mediator changes between groups using hierarchical cluster analysis. Clusters shown were either (A) significantly higher in Low n-3-fed mice; (B) significantly higher in High n-3 fed mice; (C) or had a significant diet by chemo interaction. Data presented as group means ± SEM (n = 4/group). Differences in cluster means were determined using variables as the fixed effect and subject as a random effect. One-way MANOVA was used for the variables with no interaction. Two-way MANOVA with Tukey post testing was used for the variables with significant interaction between diet and chemo (different lowercase letters denote differences in group means). Veh—saline vehicle injections; Chemo—9 mg/kg anthracycline + 90 mg/kg cyclophosphamide injections; Low n-3—0 g/kg EPA + DHA diet; High n-3—12.2 g/kg EPA + DHA diet (~2% kcal). Group means for all measured lipid mediators can be found in Tables S3–S5.

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  Figure 4. The ratios of the EPA-derived 17,18 (A) or 14,15 (B) vicinal diol to their corresponding epoxide. Data presented as group means ± SEM (n = 4/group). A two-way ANOVA with an interaction was used to detect the differences between groups. Veh—saline vehicle injections; Chemo—9 mg/kg anthracycline + 90 mg/kg cyclophosphamide injections; Low n-3—0 g/kg EPA + DHA diet; High n-3—12.2 g/kg EPA + DHA diet (~2% kcal).

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  Figure 5. The heart mitochondrial-related gene expression of (A) Ppargc1a, (B) Ppargc1b, (C) Nrf1, (D) Tfam, (E) Bax, and (F) Bcl2. Data presented as group means ± SEM (n = 5/group). A two-way ANOVA with a diet x chemo interaction was used to detect the differences between groups while pairwise comparisons were performed using a Tukey’s post hoc test. Group means with different lowercase letters were different at p < 0.05. Veh—saline vehicle injections; Chemo—9 mg/kg anthracycline + 90 mg/kg cyclophosphamide injections; Low n-3—0 g/kg EPA + DHA diet; High n-3—12.2 g/kg EPA + DHA diet (~2% kcal).