The Effects of Neuropeptide Y Overexpression on the Mouse Model of Doxorubicin-Induced Cardiotoxicity

Figures

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  Fig. 1. Body weight and composition in saline and doxorubicin (DOX) -treated wild-type (WT) and NPY-OEDβH (NPY-OE) mice (n = 7–9/group), a body weight gain in 6 weeks, b fat mass gain, and c lean mass gain. Values are presented as means ± SEM. *** p < 0.001 DOX vs. saline, ## p < 0.01 NPY vs. WT. a Two-way ANOVA genotype and treatment effects, b two-way ANOVA treatment effect, c Tukey post hoc test following two-way ANOVA

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  Fig. 2. Echocardiography data in saline- and doxorubicin (DOX) -treated wild-type (WT) and NPY-OEDβH (NPY-OE) mice (n = 7–8/group), a Ejection fraction (EF), b fractional shortening (FS), c left ventricle internal diameter, diastole (LVID, diastole), d left ventricle internal diameter, systole (LVID, systole), e interventricular septum, diastole (IVSd), f interventricular septum, systole (IVSs), g left ventricle mass (LV mass). Values are presented as means ± SEM. DOX vs. saline, two-way ANOVA treatment effect p = 0.056, p = 0.050; NPY-OE vs. WT, two-way ANOVA genotype effect p = 0.066; DOX-treated NPY-OE vs WT, t-test p = 0.084, p = 0.086

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  Fig. 3. Examples of histological findings in the paraffin sections of the heart stained with hematoxylin/eosin and Van Gieson’s staining, a normal, saline-treated mouse; 10× zoom, b normal, saline-treated mouse; 40× zoom, c–e doxorubicin-treated mouse; 40× zoom. Scale bar indicates 100 µm length

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  Fig. 4. Relative mRNA expression level in the heart in saline and doxorubicin (DOX) -treated wild-type (WT) and NPY-OEDβH (NPY-OE) mice (n = 7–8/group), a neuropeptide Y (Npy) level and b neuropeptide Y 1 receptor (Npy1R) level. Values are presented as means ± SEM, ### p < 0.001, NPY-OE vs. WT, two-way ANOVA genotype effect

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  Fig. 5. Relative mRNA expression levels of genes modifying calcium cycling system in the heart in saline- and doxorubicin (DOX) -treated wild-type (WT) and NPY-OEDβH (NPY-OE) mice (n = 5–8/group), a sarcoplasmic reticulum Ca2+ ATPase (Serca2a) level, b ryanodine receptor (RyR2) level, c phospholamban (Pln) level. Values are presented as means ± SEM, * p < 0.05 for DOX vs. Saline, two-way ANOVA treatment effect; p = 0.088 for NPY-OE vs WT, two-way ANOVA genotype effect

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  Fig. 6. Relative mRNA expression levels of cardiomyopathy marker genes in the heart in saline- and doxorubicin (DOX) -treated wild-type (WT) and NPY-OEDβH (NPY-OE) mice (n = 5–8/group), a atrial natriuretic peptide (Anp) level, b matrix metalloproteinase 2 (Mmp2) level, c matrix metalloproteinase 9 (Mmp9) level. Values are presented as means ± SEM, * p < 0.05, ** p < 0.01, p = 0.075, DOX vs. saline, two-way ANOVA treatment effect

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  Fig. 7. Relative mRNA expression levels of a tyrosine hydroxylase (Th), b β-myosin heavy chain (Mhc-β) in the hearts in saline- and doxorubicin (DOX) -treated wild-type (WT) and NPY-OEDβH (NPY-OE) mice (n = 6–8/group). Values are presented as means ± SEM, p = 0.065 DOX vs. saline, two-way ANOVA treatment effect; # p < 0.05, NPY-OE vs. WT, two-way ANOVA genotype effect