0483 : HFE gene knock-out induce cardiac dysfunction in a mouse model of hereditary hemochromatosis

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Mechanisms involved in cardiac dysfunction induced by iron overload are not fully elucidated. The goal of our study is to evaluate cardiac function in HFE gene knock-out mice and determine the potential mechanisms involved in cardiac dysfunction. Male wild type (WT, n=9), HFE gene knock-out (KO, n=8) and HFE heterozygote (Hete, n=9) mice were used in this study. Body composition (nuclear magnetic resonance) and cardiac function (echocardiography) were assessed at 7 and 20 months. Mice were sacrificed and hearts were stored at –80°C. Repeated measures ANOVA and Wilcoxon's test were performed. Differences were considered statistically significant at p<0.05. The corporal mass of HFE KO mice was significantly higher than WT and Hete mice at 7 months (respectively in g: 32.3±3.1 vs. 28.3±2.3, p<0.01 vs. 26.4±1.5, p<0.001) and at 20 months (32.7±5.2 vs. 30.4±2.9, p<0.05 vs. 28.2±1.9, p<0.01). The muscle mass was also significantly higher in HFE KO mice at 7 months (+19% vs. WT and Hete mice, p<0.001) and at 20 months (+12% vs. WT and Hete mice, p<0.05). Left ventricle end-systolic volumes were significantly greater in HFE KO mice than WT and Hete mice at 7 months (in mL: 0.043±0.008 vs. 0.022±0.004, p<0.01 vs. 0.036±0.012, p<0.01) and at 20 months (0.083±0.041 vs. 0.050±0.017, p<0.01 vs. 0.074±0.025, p<0.01). The left ventricle end-systolic diameters where higher in HFE KO mice at both 7 and 20 months compared to WT and Hete mice. The shortening fraction was significantly reduced at 7 months compared to WT (–7%, p<0.01) but not Hete mice and was significantly reduced at 20 months compared to WT (–10%, p<0.01) and Hete (–2%, p<0.01) mice. Our study showed that HFE KO mice exhibit cardiac dysfunctions and myocardial structural modifications at 7 and 20 months. Analyses of heart tissues are currently under progress to determine the potential mechanisms involved in these cardiac dysfunctions. The author hereby declares no conflict of interest