TY - JOUR
T1 - Impact of exercise training on myostatin expression in the myocardium and skeletal muscle in a chronic heart failure model
AU - Lenk, Karsten
AU - Schur, Robert
AU - Linke, Axel
AU - Erbs, Sandra
AU - Matsumoto, Yasuharu
AU - Adams, Volker
AU - Schuler, Gerhard
PY - 2009/4
Y1 - 2009/4
N2 - AimsIn late-stage chronic heart failure (CHF), elevated cytokines and cachexia are often observed. Several studies have shown that exercise training exerts beneficial effects on skeletal muscle in this setting. Furthermore, it has been shown that the expression of myostatin, a key regulator of skeletal muscle mass, is increased in a variety of cachectic states. This study aimed to investigate the expression of myostatin in CHF, the influence of exercise training on myostatin levels, and regulation of myostatin by tumour necrosis factor-α (TNF-α).Methods and resultsIn an animal model of CHF (LAD-ligation model), protein expression of myostatin was elevated 2.4-fold in the skeletal muscle and more than four-times in the myocardium, compared with control (Co). Exercise training on a treadmill over 4 weeks led to a significant reduction in myostatin protein expression in the skeletal muscle and the myocardium of CHF animals, with values returning to baseline levels. In differentiated C2C12 cells, TNF-α induced the expression of myostatin through a p38MAPK-dependent pathway involving nuclear factor kappa-B (NF-κB). The increased TNF-α mRNA levels in the skeletal muscle of CHF animals correlated significantly with myostatin expression.ConclusionThese alterations in myostatin expression in the skeletal and heart muscle following exercise training could help to explain the beneficial anti-catabolic effects of exercise training in CHF.
AB - AimsIn late-stage chronic heart failure (CHF), elevated cytokines and cachexia are often observed. Several studies have shown that exercise training exerts beneficial effects on skeletal muscle in this setting. Furthermore, it has been shown that the expression of myostatin, a key regulator of skeletal muscle mass, is increased in a variety of cachectic states. This study aimed to investigate the expression of myostatin in CHF, the influence of exercise training on myostatin levels, and regulation of myostatin by tumour necrosis factor-α (TNF-α).Methods and resultsIn an animal model of CHF (LAD-ligation model), protein expression of myostatin was elevated 2.4-fold in the skeletal muscle and more than four-times in the myocardium, compared with control (Co). Exercise training on a treadmill over 4 weeks led to a significant reduction in myostatin protein expression in the skeletal muscle and the myocardium of CHF animals, with values returning to baseline levels. In differentiated C2C12 cells, TNF-α induced the expression of myostatin through a p38MAPK-dependent pathway involving nuclear factor kappa-B (NF-κB). The increased TNF-α mRNA levels in the skeletal muscle of CHF animals correlated significantly with myostatin expression.ConclusionThese alterations in myostatin expression in the skeletal and heart muscle following exercise training could help to explain the beneficial anti-catabolic effects of exercise training in CHF.
KW - Chronic heart failure
KW - Exercise training
KW - Heart muscle
KW - Myostatin
KW - Skeletal muscle
KW - TNF-α
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U2 - 10.1093/eurjhf/hfp020
DO - 10.1093/eurjhf/hfp020
M3 - Article
C2 - 19218333
AN - SCOPUS:66249091925
VL - 11
SP - 342
EP - 348
JO - European Journal of Heart Failure
JF - European Journal of Heart Failure
SN - 1388-9842
IS - 4
ER -