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Background

The heart is 1 of the organs most affected by hereditary hemochromatosis (HH). The clinical impact of cardiomyopathy in patients with HH requires a particular diagnosis and less invasive treatments. We developed a model of cardiomyopathy in knockout (KO) mice for the high-Fe (HFE) gene and assessed left ventricular (LV) function and structure from 7-20 months.

Methods

Male wild-type (WT) heterozygous and KO SV129 mice for the HFE gene were used in this study. Twenty-four mice were used to assess LV function and structure by echocardiography at 7, 14, 18, and 20 months. Evaluations of LV function and structure and myocardial fibrosis were performed at 7 and 20 months.

Results

The percent decrease of LV thickness-to-radius ratio between 7 and 20 months was higher in KO mice compared with WT mice (-30.2% ± 5.3% vs -10.5% ± 4.9%; P < 0.01). The LV diameters were higher in old mice compared with young mice (+13% at end-diastole; +33% at end-systole; P < 0.001). The LV ejection fraction values were lower in KO mice compared with WT mice between 7 and 20 months. The highest difference was found at 14 months (60.0% ± 7.6% vs 78.1% ± 3.5%; P < 0.001). Myocardial fibrosis was higher in old KO mice compared with old WT mice (+55%; P < 0.001), and myocardial iron deposition was slightly increased in old KO mice compared with old WT mice (1.31% ± 0.33% vs 0.84% ± 0.22%; P = 0.056).

Conclusions

The present mouse model has the potential to allow the determination of underlying mechanisms involved in the cardiomyopathy induced by HFE-related hemochromatosis."xsd:string
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http://purl.uniprot.org/citations/28558946http://purl.uniprot.org/core/author"Toussaint J.F."xsd:string
http://purl.uniprot.org/citations/28558946http://purl.uniprot.org/core/author"Trzaskus Y."xsd:string
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http://purl.uniprot.org/citations/28558946http://purl.uniprot.org/core/name"Can J Cardiol"xsd:string
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http://purl.uniprot.org/citations/28558946http://purl.uniprot.org/core/title"A Mouse Model of Cardiomyopathy Induced by Mutations in the Hemochromatosis HFE Gene."xsd:string
http://purl.uniprot.org/citations/28558946http://purl.uniprot.org/core/volume"33"xsd:string
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