Impact of exercise training on myostatin expression in the myocardium and skeletal muscle in a chronic heart failure model.
OBJECTIVE
In 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-alpha (TNF-alpha).


RESULTS
In 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-alpha induced the expression of myostatin through a p38MAPK-dependent pathway involving nuclear factor kappa-B (NF-kappaB). The increased TNF-alpha mRNA levels in the skeletal muscle of CHF animals correlated significantly with myostatin expression.


CONCLUSIONS
These 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.
Lenk
Karsten
K
Clinic of Cardiology, University Leipzig-Heart Center Leipzig, Strümpellstrasse 39, D-04289 Leipzig, Germany. karsten.lenk@med.uni-leipzig.de
Schur
Robert
R
Linke
Axel
A
Erbs
Sandra
S
Matsumoto
Yasuharu
Y
Adams
Volker
V
Schuler
Gerhard
G
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005081:Exercise Therapy / Q000379:methods*; D015870:Gene Expression; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000534:rehabilitation*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D055435:Myostatin / Q000096:biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D051381:Rats; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D055435:Myostatin; D014409:Tumor Necrosis Factor-alpha; D012313:RNA