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The Huntington's disease-related cardiomyopathy prevents a hypertrophic response in the R6/2 mouse model.
Mielcarek, Michal; Bondulich, Marie K; Inuabasi, Linda; Franklin, Sophie A; Muller, Thomas; Bates, Gillian P.
Afiliación
  • Mielcarek M; Department of Medical and Molecular Genetics, King's College London, London, United Kingdom.
  • Bondulich MK; Department of Medical and Molecular Genetics, King's College London, London, United Kingdom.
  • Inuabasi L; Department of Medical and Molecular Genetics, King's College London, London, United Kingdom.
  • Franklin SA; Department of Medical and Molecular Genetics, King's College London, London, United Kingdom.
  • Muller T; Department of Medical and Molecular Genetics, King's College London, London, United Kingdom.
  • Bates GP; Department of Medical and Molecular Genetics, King's College London, London, United Kingdom.
PLoS One ; 9(9): e108961, 2014.
Article en En | MEDLINE | ID: mdl-25268775
Huntington's disease (HD) is neurodegenerative disorder for which the mutation results in an extra-long tract of glutamines that causes the huntingtin protein to aggregate. It is characterized by neurological symptoms and brain pathology that is associated with nuclear and cytoplasmic aggregates and with transcriptional deregulation. Despite the fact that HD has been recognized principally as a neurological disease, there are multiple epidemiological studies showing that HD patients exhibit a high rate of cardiovascular events leading to heart failure. To unravel the mechanistic basis of cardiac dysfunction in HD, we employed a wide range of molecular techniques using the well-established genetic R6/2 mouse model that develop a considerable degree of the cardiac atrophy at end stage disease. We found that chronic treatment with isoproterenol, a potent beta-adrenoreceptor agonist, did not change the overall gross morphology of the HD murine hearts. However, there was a partial response to the beta-adrenergenic stimulation by the further re-expression of foetal genes. In addition we have profiled the expression level of Hdacs in the R6/2 murine hearts and found that the isoproterenol stimulation of Hdac expression was partially blocked. For the first time we established the Hdac transcriptional profile under hypertrophic conditions and found 10 out of 18 Hdacs to be markedly deregulated. Therefore, we conclude that R6/2 murine hearts are not able to respond to the chronic isoproterenol treatment to the same degree as wild type hearts and some of the hypertrophic signals are likely attenuated in the symptomatic HD animals.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Huntington / Cardiomiopatías / Miocardio Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2014 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Huntington / Cardiomiopatías / Miocardio Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2014 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos