Impact of exercise training on myostatin expression in the myocardium and skeletal muscle in a chronic heart failure model
Impact of exercise training on myostatin expression in the myocardium and skeletal muscle in a chronic heart failure model
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DOI：
10.1093/eurjhf/hfp020
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发表时间：
2009-04-01
影响因子：
18.2
通讯作者：
Schuler, Gerhard
中科院分区：
文献类型：
--
作者：
Lenk, Karsten;Schur, Robert;Schuler, Gerhard
在晚期慢性心力衰竭（CHF）中，经常观察到细胞因子升高和恶病质。一些研究表明，运动训练在这种情况下对骨骼肌产生有益的影响。此外，已经表明，肌肉生长抑制素（骨骼肌质量的关键调节物）的表达在各种恶病质状态下增加。本研究旨在探讨心肌生长抑制素（myostatin）在慢性心力衰竭（CHF）中的表达、运动训练对myostatin水平的影响以及肿瘤坏死因子-α（TNF-α）对myostatin的调节作用。在跑步机上进行4周以上的运动训练导致CHF动物骨骼肌和心肌中肌生长抑制素蛋白表达显著减少，值恢复到基线水平。在分化的C2 C12细胞中，TNF-α通过涉及核因子κ-B（NF-κ B）的p38 MAPK依赖性途径诱导肌生长抑制素的表达。CHF动物骨骼肌中TNF-α mRNA水平的增加与肌肉生长抑制素表达显著相关，这些运动训练后骨骼肌和心肌中肌肉生长抑制素表达的改变有助于解释运动训练对CHF的有益抗分解代谢作用。
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).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.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.