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European Journal of Heart Failure Advance Access originally published online on February 13, 2009
European Journal of Heart Failure 2009 11(4):342-348; doi:10.1093/eurjhf/hfp020
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Impact of exercise training on myostatin expression in the myocardium and skeletal muscle in a chronic heart failure model

Karsten Lenk*, Robert Schur, Axel Linke, Sandra Erbs, Yasuharu Matsumoto, Volker Adams and Gerhard Schuler

Clinic of Cardiology, University Leipzig—Heart Center Leipzig, Strümpellstrasse 39, D-04289 Leipzig, Germany

* Corresponding author. Tel: +49 341 865 1671, Fax: +49 341 865 1461, Email: karsten.lenk{at}med.uni-leipzig.de


  Abstract

Aims: 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}).

Methods and 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-{kappa}B). The increased TNF-{alpha} mRNA levels in the skeletal muscle of CHF animals correlated significantly with myostatin expression.

Conclusion: 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.

Key Words: Myostatin • Exercise training • Chronic heart failure • Heart muscle • Skeletal muscle • TNF-{alpha}

Received July 1, 2008; Revised October 16, 2008; Accepted November 17, 2008


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