Mitochondria and heart failure.
OBJECTIVE
Energetic abnormalities in cardiac and skeletal muscle occur in heart failure and correlate with clinical symptoms and mortality. It is likely that the cellular mechanism leading to energetic failure involves mitochondrial dysfunction. Therefore, it is crucial to elucidate the causes of mitochondrial myopathy, in order to improve cardiac and skeletal muscle function, and hence quality of life, in heart failure patients.


RESULTS
Recent studies identified several potential stresses that lead to mitochondrial dysfunction in heart failure. Chronically elevated plasma free fatty acid levels in heart failure are associated with decreased metabolic efficiency and cellular insulin resistance. Tissue hypoxia, resulting from low cardiac output and endothelial impairment, can lead to oxidative stress and mitochondrial DNA damage, which in turn causes dysfunction and loss of mitochondrial mass. Therapies aimed at protecting mitochondrial function have shown promise in patients and animal models with heart failure.


CONCLUSIONS
Despite current therapies, which provide substantial benefit to patients, heart failure remains a relentlessly progressive disease, and new approaches to treatment are necessary. Novel pharmacological agents are needed that optimize substrate metabolism and maintain mitochondrial integrity, improve oxidative capacity in heart and skeletal muscle, and alleviate many of the clinical symptoms associated with heart failure.
Murray
Andrew J
AJ
Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK. andrew.james.murray@gmail.com [corrected]
Edwards
Lindsay M
LM
Clarke
Kieran
K
D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D011788:Quality of Life