Pathophysiology of peripheral muscle wasting in cardiac cachexia

Abstract

Many hypotheses have been used to explain the pathogenesis of muscle wasting in cardiac cachexia. Cardiac cachexia is a multifactorial disorder, and the targeting of different pathways will be necessary for effective treatment. The immune and neurohormonal abnormalities present in chronic heart failure may play a significant role in the pathogenesis of the wasting process. It has been suggested that common pathogenetic mechanisms underlie the loss of muscle mass in different cachectic states. More studies are needed to show whether there is a common pathway in cardiac cachexia and the other cachectic states.

Atorvastatin modulates constitutive and lipopolysaccharide induced IL-6 secretion in precursors of human skeletal muscle

“…More recently, myocytes have raised a lot of interest as 'endocrine' cells, as it has been demonstrated that they can produce several signalling molecules, including, in particular, the cytokines with IL-6 constitutively secreted, and also produced in response to various stress stimuli (Pedersen et al, 2001;Filippatos et al, 2005;Prelovsek et a., 2006;Shang et al, 2006). Primary cultures of human myotubes were used here as an in-vitro model for human skeletal muscle.…”

“…Indeed, this local production of cytokines in skeletal muscle and myocardium in response to stressors (LPS, exercise and hypoxia) can be abundant, and can contribute substantially to the amounts of these cytokines in the systemic circulation, mimicking the responses generally observed in inflammatory disease (Febbraio and Pedersen, 2002;Prabhu, 2004;Prelovsek et al, 2006;Brandt and Pedersen, 2010;Pirkmajer et al, 2011). Recent studies have revealed a strong involvement of skeletal muscle in the pathophysiology of chronic disease and its role as an important target and generator of detrimental pathophysiological processes (Filippatos et al, 2005).…”

Anti-TNF treatment reduces rat skeletal muscle wasting in monocrotaline-induced cardiac cachexia

“…Both inflammation and anorexia can independently contribute to skeletal muscle wasting. Cachexia associated with congestive heart failure (CHF), or cardiac cachexia, has a 50% mortality rate at 18 mo for the 10 -16% of CHF patients diagnosed as cachectic (2).Increased protein degradation by the ubiquitin-proteasome pathway (UPP) is implicated in skeletal muscle wasting in cachectic conditions (15,29). In those cachectic states investigated to date, UPP activity is upregulated in skeletal muscle; transcript levels for UPP members are also upregulated 8-, 2-, 40-, and 8-fold for ubiquitin, E2 ubiquitin conjugating enzymes, E3 ubiquitin ligases, and subunits of the 26S proteasome, respectively (4, 6, 15).…”

High‐Intensity Resistance Training with Insufficient Recovery Time Between Bouts Induce Atrophy and Alterations in Myosin Heavy Chain Content in Rat Skeletal Muscle

“…With skeletal muscle atrophy, myonuclei numbers decrease, decreasing DNA units in overtrained muscle, thereby decreasing synthesis and increasing degradation rate of muscle proteins; this promotes the development of overtraining myopathy (Seene et al, 1999). Although the mechanisms responsible for muscle atrophy are not completely defined, several factors seem to be involved; these include reduced neuromuscular activity, systemic activation of neurohormones and inflammatory cytokines (Dalla Libera et al, 2001;Filippatos et al, 2005), myostatin/follistatin imbalance (Lima et al, 2010), and ubiquitin-proteasome pathway activation (Schulze and Upä te, 2005). The ubiquitin-proteasomal pathway, which includes the muscle-specific E3 ligases, atrogin-1/muscle atrophy F-box (MAFbx), and muscle RING Finger 1 (MuRF1), is known to be a powerful contributor to muscle proteolysis (Bodine et al, 2001;Gomes et al, 2001).…”