Sexual dimorphism in acute myocardial infarction-induced acute kidney injury: cardiorenal deteriorating effects of ovariectomy in premenopausal female mice

Figures

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  Figure 1. Comparison of EF between MMI and FMI mice, and between FMI and FMIOVX EF markedly decreased in MI mice of both sexes compared with their relative control groups (A). EF significantly decreased in FMIOVX mice compared with the FMI group (B). Data were analyzed for MMI and FMI using two-way ANOVA, and for FMI and FMIOVX using unpaired t-test. All bars represent mean ± SEM (*P<0.05; n=4–13); MI, myocardial infarction; OVX, ovariectomy.

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  Figure 2. Glomerular alterations in MMI, FMI, and FMIOVX mice Glomerular retraction and the Bowman’s capsule area markedly increased in MI males, but not in MI females (A,B). Glomerular capillary area decreased in MI male mice but not MI females (C). There was no change in glomerular retraction, Bowman’s capsule area, and glomerular capillary in FMIOVX mice compared with FMI mice (D–F). Representative image of each stained group is shown. Data were analyzed for MMI and FMI using two-way ANOVA, and for FMI and FMIOVX by unpaired t-test. All bars represent mean ± SEM (*P<0.05, n=3–7).

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  Figure 3. PCT-CSA comparison among MMI, FMI, and FMIOVX mice PCT-CSA significantly increased with MI in male mice compared with females (A). PCT-CSA substantially increased in FMIOVX mice compared with the FMI group (B). Data were analyzed for MMI and FMI using two-way ANOVA, and for FMI and FMIOVX by unpaired t-test. All bars represent mean ± SEM (*P<0.05, n=3–7).

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  Figure 4. Renal cytokine and caspase-3 comparisons in MMI, FMI, and FMIOVX mice IL-1β protein levels significantly increased in the kidneys of MI male mice compared with their controls (A). Uncleaved caspase-3 markedly increased in the kidneys of MI male mice but not in females (B). IL-4 protein levels substantially increased in the kidneys of MI male mice compared with their controls groups (C). IL-1β but not caspase-3 and IL-4 substantially increased in FMIOVX mice compared with the FMI group (D–F). Representative image of each blot is shown. IL-1β and caspase-3 protein levels were normalized to total protein (Supplementary Figure S1). Data were analyzed for MMI and FMI using two-way ANOVA, and for FMI and FMIOVX using unpaired t-test. All bars represent mean ± SEM (*P<0.05, n=3–5).

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  Figure 5. Comparison of NAD+ biosynthetic enzymes and total renal NAD levels between MMI and FMI mice, and between FMI and FMIOVX NAMPT and NMRK-1 mRNA expression levels significantly increased in the kidneys of MI female mice compared with the relative male group (A,B). Total renal NAD levels decreased in both sexes with MI (C). NAMPT mRNA expression levels decreased in the kidneys of FMIOVX mice compared with the FMI group (D), whereas NMRK-1 mRNA expression levels significantly increased in the kidneys of FMIOVX mice compared with the FMI group (E). No significant change in total NAD levels in the kidneys of FMIOVX mice compared with the FMI group was observed (F). Data were analyzed for MMI and FMI using two-way ANOVA, and for FMI and FMIOVX using unpaired t-test. All bars represent mean ± SEM (*P<0.05).

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  Figure 6. The effects of MI and OVX on PARP-1 in the kidney PARP-1 mRNA expression levels significantly increased in the kidneys of male mice with MI compared with females (A). No significant increase in PARP-1 mRNA expression levels was observed in the kidneys of FMIOVX mice compared with the FMI group (B). Data were analyzed for MMI and FMI using two-way ANOVA, and for FMI and FMIOVX using unpaired t-test. All bars represent mean ± SEM (*P<0.05).

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  Figure 7. The effects of MI and OVX on α-SMA protein levels α-SMA protein significantly increased in the kidneys of MI male unlike females (A). No significant change in α-SMA protein levels in the kidneys of FMIOVX mice compared with the FMI group was observed (B). α-SMA protein levels were normalized to total protein (Supplementary Figure S3). Data were analyzed for MMI and FMI using two-way ANOVA, and for FMI and FMIOVX using unpaired t-test. All bars represent mean ± SEM (*P<0.05, n=3–4).

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  Figure 8. The effects of MI and OVX on total renal fibrosis Total renal fibrosis significantly increased in male mice with MI compared with females (A). Total renal fibrosis increased in FMIOVX mice compared with the FMI group (B). Representative image of each MTC stained group is shown. Data were analyzed for MMI and FMI using two-way ANOVA, and for FMI and FMIOVX using unpaired t-test. All bars represent mean ± SEM (*P<0.05, n=3–7).

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  Figure 9. Effects of MI and OVX on CrCl, urine output, and urine protein concentration CrCl was decreased with MI mice in both sexes (A). Urine output was markedly decreased in MI male mice compared with controls (B). No change in urine protein concentration with MI mice of both sexes was observed (C). CrCl and urine output decreased in FMIOVX mice compared with the FMI group (D,E), whereas no change was observed in urine protein concentration in FMIVX mice compared with the FMI group (F). Data were analyzed for MMI and FMI using two-way ANOVA, and for FMI and FMIOVX using unpaired t-test. All bars represent mean ± SEM (*P<0.05, n=3–9).