Sex differences and estrogen effects in cardiac mitochondria in human aortic stenosis and in the mouse heart

Figures

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  Figure 1. Schematical hypothesis. Main research questions are labeled in orange, main results in grey. Figures at the left depict source of material, figure at the right depicts an exemplary mitochondrial measurement using an oxygraph system. Oxygen consumption was measured in triple.

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  Figure 2. Study design of in vivo mouse experiments. Female and male mice at the age of 8 weeks were gonadectomized. Fourteen days after the surgical procedure, the animals were treated once intraperitoneally with vehicle (placebo), estrogen (E2), or with a specific ERα or ERβ agonist. After 24 h, the hearts and the musculus soleus were removed for the measurement of mitochondrial respiration. OVX, ovariectomy; ORX, orchidectomy; E2, 17β-estradiol; ER, estrogen receptor; IP, intraperitoneal.

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  Figure 3. Uterine weights of female mice. Uterine weights are depicted in mg. OVX, ovariectomy; ORX, orchidectomy; E2, 17β- estradiol; ERβ agonist, estrogen receptor beta agonist; ERα agonist, estrogen receptor alpha agonist (PPT, propyl pyrazole triol). One-way ANOVA and Šídák’s multiple comparisons test; *p< 0.05 significant to intact placebo group (female), #p< 0.05 significant to OVX placebo group, n = 8/group. Data present mean ± SEM.

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  Figure 4. State-3 respiration in cardiac skinned fibers in female (red column) and male (blue column) human hearts. Substrates glutamate and malate (Glu/Mal) were used for the mitochondrial measurements. Oxygen consumption of State-3 respiration is depicted in nmol/mL/min/mg dry weight. dw, dry weight; RCI, respiratory control index. One -sample t-test and Wilcoxon test. *p< 0.05 significant to intact placebo group (female), n = 8/group. Data present mean ± SEM.

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  Figure 5. State-3 respiration in cardiac skinned fibers in female (A) and male (B) mice and skeletal muscle skinned fibers in female (C) and male (D) mice. Substrates glutamate and malate (Glu/Mal) were used for the mitochondrial measurements. Oxygen consumption of State-3 respiration is depicted in nmol/mL/min/mg dry weight. dw, dry weight; OVX, ovariectomy; ORX, orchidectomy; E2, 17 β -estradiol; ERβ, estrogen receptor beta; ERα agonist, estrogen receptor beta (PPT, propyl pyrazole triol). ANOVA and Šídák’s multiple comparisons test; *p ≤ 0.05 significant to Intact placebo group (female) and Intact placebo group (males), #p< 0.05 significant to OVX placebo group females and ORX placebo group (males), n = 8/group. Data present mean ± SEM.