Skeletal muscle apoptosis in experimental heart failure: the only link between inflammation and skeletal muscle wastage?

Purpose of review The purpose of this review is to enlighten the mechanisms of muscle wastage in experimental heart failure with attention to skeletal muscle apoptosis and the role of proinflammatory cytokines that trigger apoptosis. Recent findings Mechanisms leading to muscle wastage in chronic heart failure include cytokine-triggered skeletal muscle apoptosis, but also ubiquitin/proteasome and non-ubiquitin-dependent pathways. The regulation of fibre type involves the growth hormone/insulin-like growth factor 1 /calcineurin/ transcriptional coactivator PGC1 cascade. Summary Several mechanisms can lead to muscle wastage in heart failure. The imbalance between protein synthesis and degradation plays an important role. Protein degradation can occur through ubiquitin-dependent and non-ubiquitin-dependent pathways. Systems controlling ubiquitin/ proteasome activation have been described. These are triggered by tumour necrosis factor a and growth hormone/ insulin-like growth factor 1. However, an important role is played by apoptosis. In humans and experimental models of heart failure programmed cell death has been found in skeletal muscle and interstitial cells. Apoptosis is triggered by turnout necrosis factor alpha and in-vitro experiments have shown that it can be induced by its second messenger sphingosine. Apoptosis correlates with the severity of the heart failure syndrome. It involves activation of caspases 3 and 9 and mitochondrial cytochrome c release.