Muscle wastage in chronic heart failure, between apoptosis, catabolism and altered anabolism: a chimaeric view of inflammation?

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Purpose of the review

The mechanisms involved in determining skeletal muscle wastage and cachexia in heart failure are complex and not unequivocal. There are however three different mechanisms that are in some way related to each other and play a very important role. These are inflammation, the catabolic/anabolic imbalance and apoptosis. We have tried to link these pathophysiological processes with the aim of giving a holistic view.

Recent findings

Recent experiments have demonstrated that a major determinant of muscle atrophy in congestive heart failure is apoptosis of skeletal myocytes. Apoptosis is triggered by tumour necrosis factor α and its second messenger sphingosine. The source of tumour necrosis factor α has to be searched for in inflammation, which may have its origin in the bowel, in the heart, in peripheral hypoxic tissues or in neurohormonal activation. It has also been shown that the growth hormone/insulin-like growth factor 1 axis regulates contractile protein synthesis (transition from slow to fast fibres) and apoptosis, through calcineurin, FK506-FK506-binding protein, mitogen-activated protein kinase and nuclear factor κB. Tumour necrosis factor α also intervenes in this interplay by activating nuclear factor κB.


According to these new pathophysiological insights, some strategies aiming to prevent or revert congestive heart failure myopathy with pharmacological interventions blocking inflammation, tumour necrosis factor α and apoptosis have been proposed. Future perspectives are based on stem cell implantation, transcription and gene therapy, for instance by overexpression of insulin-like growth factor 1.

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