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Metabolic Alterations in Cardiomyocytes of Patients with Duchenne and Becker Muscular Dystrophies

Duchenne and Becker muscular dystrophies (DMD/BMD) result in progressive weakness of skeletal and cardiac muscles due to the deficiency of functional dystrophin. Respiratory failure is a leading cause of mortality in DMD patients; however, improved management of the respiratory symptoms have increas...

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Autores principales: Esposito, Gabriella, Carsana, Antonella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947625/
https://www.ncbi.nlm.nih.gov/pubmed/31817415
http://dx.doi.org/10.3390/jcm8122151
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author Esposito, Gabriella
Carsana, Antonella
author_facet Esposito, Gabriella
Carsana, Antonella
author_sort Esposito, Gabriella
collection PubMed
description Duchenne and Becker muscular dystrophies (DMD/BMD) result in progressive weakness of skeletal and cardiac muscles due to the deficiency of functional dystrophin. Respiratory failure is a leading cause of mortality in DMD patients; however, improved management of the respiratory symptoms have increased patients’ life expectancy, thereby also increasing the clinical relevance of heart disease. In fact, the prevalence of cardiomyopathy, which significantly contributes to mortality in DMD patients, increases with age and disease progression, so that over 95% of adult patients has cardiomyopathy signs. We here review the current literature featuring the metabolic alterations observed in the dystrophic heart of the mdx mouse, i.e., the best-studied animal model of the disease, and discuss their pathophysiological role in the DMD heart. It is well assessed that dystrophin deficiency is associated with pathological alterations of lipid metabolism, intracellular calcium levels, neuronal nitric oxide (NO) synthase localization, and NO and reactive oxygen species production. These metabolic stressors contribute to impair the function of the cardiac mitochondrial bulk, which has a relevant pathophysiological role in the development of cardiomyopathy. In fact, mitochondrial dysfunction becomes more severe as the dystrophic process progresses, thereby indicating it may be both the cause and the consequence of the dystrophic process in the DMD heart.
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spelling pubmed-69476252020-01-13 Metabolic Alterations in Cardiomyocytes of Patients with Duchenne and Becker Muscular Dystrophies Esposito, Gabriella Carsana, Antonella J Clin Med Review Duchenne and Becker muscular dystrophies (DMD/BMD) result in progressive weakness of skeletal and cardiac muscles due to the deficiency of functional dystrophin. Respiratory failure is a leading cause of mortality in DMD patients; however, improved management of the respiratory symptoms have increased patients’ life expectancy, thereby also increasing the clinical relevance of heart disease. In fact, the prevalence of cardiomyopathy, which significantly contributes to mortality in DMD patients, increases with age and disease progression, so that over 95% of adult patients has cardiomyopathy signs. We here review the current literature featuring the metabolic alterations observed in the dystrophic heart of the mdx mouse, i.e., the best-studied animal model of the disease, and discuss their pathophysiological role in the DMD heart. It is well assessed that dystrophin deficiency is associated with pathological alterations of lipid metabolism, intracellular calcium levels, neuronal nitric oxide (NO) synthase localization, and NO and reactive oxygen species production. These metabolic stressors contribute to impair the function of the cardiac mitochondrial bulk, which has a relevant pathophysiological role in the development of cardiomyopathy. In fact, mitochondrial dysfunction becomes more severe as the dystrophic process progresses, thereby indicating it may be both the cause and the consequence of the dystrophic process in the DMD heart. MDPI 2019-12-05 /pmc/articles/PMC6947625/ /pubmed/31817415 http://dx.doi.org/10.3390/jcm8122151 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Esposito, Gabriella
Carsana, Antonella
Metabolic Alterations in Cardiomyocytes of Patients with Duchenne and Becker Muscular Dystrophies
title Metabolic Alterations in Cardiomyocytes of Patients with Duchenne and Becker Muscular Dystrophies
title_full Metabolic Alterations in Cardiomyocytes of Patients with Duchenne and Becker Muscular Dystrophies
title_fullStr Metabolic Alterations in Cardiomyocytes of Patients with Duchenne and Becker Muscular Dystrophies
title_full_unstemmed Metabolic Alterations in Cardiomyocytes of Patients with Duchenne and Becker Muscular Dystrophies
title_short Metabolic Alterations in Cardiomyocytes of Patients with Duchenne and Becker Muscular Dystrophies
title_sort metabolic alterations in cardiomyocytes of patients with duchenne and becker muscular dystrophies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947625/
https://www.ncbi.nlm.nih.gov/pubmed/31817415
http://dx.doi.org/10.3390/jcm8122151
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