Low dystrophin levels in heart can delay heart failure in mdx mice.
J Mol Cell Cardiol
; 69: 17-23, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24486194
ABSTRACT
Duchenne muscular dystrophy is caused by mutations that prevent synthesis of functional dystrophin. All patients develop dilated cardiomyopathy. Promising therapeutic approaches are underway that successfully restore dystrophin expression in skeletal muscle. However, their efficiency in the heart is limited. Improved quality and function of only skeletal muscle potentially accelerate the development of cardiomyopathy. Our study aimed to elucidate which dystrophin levels in the heart are required to prevent or delay cardiomyopathy in mice. Heart function and pathology assessed with magnetic resonance imaging and histopathological analysis were compared between 2, 6 and 10-month-old female mdx-Xist(Δhs) mice, expressing low dystrophin levels (3-15%) in a mosaic manner based on skewed X-inactivation, dystrophin-negative mdx mice, and wild type mice of corresponding genetic backgrounds and gender. With age mdx mice developed dilated cardiomyopathy and hypertrophy, whereas the onset of heart pathology was delayed and function improved in mdx-Xist(Δhs) mice. The ejection fraction, the most severely affected parameter for both ventricles, correlated to dystrophin expression and the percentage of fibrosis. Fibrosis was partly reduced from 9.8% in mdx to 5.4% in 10 month old mdx-Xist(Δhs) mice. These data suggest that mosaic expression of 4-15% dystrophin in the heart is sufficient to delay the onset and ameliorate cardiomyopathy in mice.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fibrose
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Biomarcadores
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Distrofina
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Distrofia Muscular de Duchenne
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Insuficiência Cardíaca
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Distrofia Muscular Animal
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
J Mol Cell Cardiol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Holanda