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

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• 作者：Ying-Han R. Hsu ; Haran Yogasundaram ; Nirmal Parajuli…
• 关键词：Cardiomyopathy ; Mitochondria ; MELAS syndrome ; HF
• 刊名：Heart Failure Reviews
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：21
• 期：1
• 页码：103-116
• 全文大小：2,339 KB
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• 作者单位：Ying-Han R. Hsu (1)
  Haran Yogasundaram (2)
  Nirmal Parajuli (2)
  Lucas Valtuille (2)
  Consolato Sergi (1)
  Gavin Y. Oudit (2)
  
  1. Department of Laboratory Medicine and Pathology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada
  2. Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, 8440 112 Street NW, Edmonton, AB, T6G 2B7, Canada
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Cardiology
  
• 出版者：Springer Netherlands
• ISSN：1573-7322

文摘

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. Keywords Cardiomyopathy Mitochondria MELAS syndrome HF