DPP-4 Inhibitor and Estrogen Share Similar Efficacy Against Cardiac Ischemic-Reperfusion Injury in Obese-Insulin Resistant and Estrogen-Deprived Female Rats

Figures

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  Figure 1. Effect of estrogen deprivation and obese-insulin resistance on left ventricular function and heart rate variability prior to pharmacological interventions. 12 weeks after ovariectomy, normal-diet fed ovariectomized rats (NDO) and high fat-diet fed ovariectomized rats (HFO) had reduced % fractional shortening (a), reduced % ejection fraction (b) and had increased LF/HF ratio (c), when compared with normal-diet fed sham operated (NDS) rats. Values are mean ± SEM for 6 rats in each group. *P < 0.05 vs. NDS.

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  Figure 2. Effect of estrogen and vildagliptin on left ventricular function and heart rate variability of estrogen-deprived rats after treatments. % Fractional shortening (a) and % ejection fraction (b) were increased in estrogen (E)- and vildagliptin (Vil)-treated rats when compared with vehicle-treated rats. LF/HF ratio (c) was increased and restored to the normal level in both E- and Vil-treated groups. Values are mean ± SEM for 6 rats per group. *P < 0.05 vs. NDS, †P < 0.05 vs. NDOVe and ‡P < 0.05 vs. HFOVe.

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  Figure 3. Cardiac arrhythmia, mortality rate and cardiac expression Cx43, after treatment with estrogen or vildagliptin for 4 weeks. Arrhythmia score (a) was decreased, and time to 1st VT/VF (b) was prolonged in both estrogen (E)- and vildagliptin (Vil)-treated groups. Post-ischemia mortality rate (c), presented in % of number of rats in each experimental group was significantly reduced following treatment with E and Vil, when compared with vehicle-treated group. The ratio of p-Cx43/total-Cx43 expressions (d) in ischemic (I) area/remote (R) area, were reduced in NDOVE and HFOVe rats, when compared with those of NDS rats. Values are mean ± SEM for 6 rats per group. *P < 0.05 vs. NDS, †P < 0.05 vs. NDOVe and ‡P < 0.05 vs. HFOVe.

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  Figure 4. The levels of infarct size and cardiac expression of apoptotic and anti-apoptotic proteins, after treatment with estrogen or vildagliptin for 4 weeks. Both NDOVE and HFOVe had increased level of infarct size (a), and both estrogen (E)- and vildagliptin (Vil)-treatment significantly diminished myocardial infarction. The representative infarcted myocardium was demonstrated in (b). Expression levels of the apoptotic protein Bax (c) were significantly increased in NDOVe and HFOVE rats, whereas the expression levels of anti-apoptotic protein, Bcl-2 (d) were reduced in HFOVe rats. The cardiac level of cytochrome C expression (e) was increased in HFOVe rats and significantly reduced by both E and Vil-treatments. Plasma LDH level (f) was significantly elevated in both NDOVe and HFOVe rats, when compared with NDS rats. The plasma level of LDH in the intervention groups was not significant different from the NDS rats. Values are mean ± SEM for 6 rats per group. *P < 0.05 vs. NDS, †P < 0.05 vs. NDOVe and ‡P < 0.05 vs. HFOVe.

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  Figure 5. Cardiac mitochondrial function in estrogen-deprived rats after treatment with estrogen or vildagliptin for 4 weeks. All mitochondrial function parameters are represented in the ratio of ischemic/remote area. Mitochondrial ROS level (a) was increased while ΔΨ (mitochondrial membrane potential change, (b) and absorbance intensity (c) were decreased in NDOVe and HFOVe rats. Transmission electron micrographs (d) illustrate cardiac mitochondria morphology of rats in each group. Treatment with estrogen and vildagliptin led to an improvement in all parameters of cardiac mitochondrial function in both NDO and HFO rats. Values are mean ± SEM for 6 rats per group. *P < 0.05 vs. NDS, †P < 0.05 vs. NDOVe and ‡P < 0.05 vs. HFOVe.