MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.

Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early p...

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Publicado en:Heart Failure Reviews Vol. 21; no. 1; pp. 103 - 117
Autores principales: Hsu, Ying-Han, Yogasundaram, Haran, Parajuli, Nirmal, Valtuille, Lucas, Sergi, Consolato, Oudit, Gavin, Hsu, Ying-Han R, Oudit, Gavin Y
Formato: research Journal Article
Publicado: Springer Nature Jan2016
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jan2016
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      pub: Springer Nature
      place: New York, New York
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        atl: MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.
      aug:
        au:
          Hsu, Ying-Han
          Yogasundaram, Haran
          Parajuli, Nirmal
          Valtuille, Lucas
          Sergi, Consolato
          Oudit, Gavin
          Hsu, Ying-Han R
          Oudit, Gavin Y
        affil: Department of Laboratory Medicine and Pathology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton Canada
      sug:
        subj:
          Mitochondrial Encephalomyopathies Physiopathology
          Myocardial Diseases Physiopathology
          Heart Failure Metabolism
          Mitochondria Metabolism
          Mitochondrial Encephalomyopathies Metabolism
          Myocardial Diseases Metabolism
          Myocardial Diseases Complications
          Mitochondrial Encephalomyopathies Complications
          Heart Failure Etiology
          Heart Failure Physiopathology
          Human
      ab: Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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