Department of Internal Medicine, Botucatu Medical School, State University of Sao Paulo-UNESP, Botucatu, Sao Paulo, Brazil.
Int J Exp Pathol. 2010 Feb;91(1):54-62. doi: 10.1111/j.1365-2613.2009.00683.x. Epub 2009 Dec 3.
Skeletal muscle abnormalities can contribute to decreased exercise capacity in heart failure. Although muscle atrophy is a common alteration in heart failure, the mechanisms responsible for muscle mass reduction are not clear. Myostatin, a member of TGF-beta family (transforming growth factor), regulates muscle growth and mass. Several studies have shown a negative correlation between myostatin expression and muscle mass. The aim of this study was to evaluate myostatin expression in skeletal muscles of rats with heart failure. As myostatin gene expression can be modulated by follistatin, we also evaluated its expression. Heart failure was induced by myocardial infarction (MI, n = 10); results were compared to Sham-operated group (n = 10). Ventricular function was assessed by echocardiogram. Gene expression was analyzed by real-time PCR and protein levels by Western blotting in the soleus and gastrocnemius muscles; fibre trophism was evaluated by morphometric analysis. MI group presented heart failure evidence such as pleural effusion and right ventricular hypertrophy. Left ventricular dilation and dysfunction were observed in MI group. In the soleus muscle, cross-sectional area (P = 0.006) and follistatin protein levels (Sham 1.00 +/- 0.36; MI 0.18 +/- 0.06 arbitrary units; P = 0.03) were lower in MI and there was a trend for follistatin gene expression to be lower in MI group (P = 0.085). There was no change in myostatin expression between groups. In gastrocnemius, all MI group parameters were statistically similar to the Sham. In conclusion, our data show that during chronic heart failure, decreased skeletal muscle trophism is combined with unchanged myostatin and reduced follistatin expression.
骨骼肌异常可能导致心力衰竭患者运动能力下降。虽然肌肉萎缩是心力衰竭的常见改变，但导致肌肉质量减少的机制尚不清楚。肌肉生长抑制素（myostatin）是转化生长因子（transforming growth factor）TGF-β家族的成员，调节肌肉生长和质量。多项研究表明肌肉生长抑制素表达与肌肉质量呈负相关。本研究旨在评估心力衰竭大鼠骨骼肌中肌肉生长抑制素的表达。由于肌肉生长抑制素基因表达可被卵泡抑素（follistatin）调节，我们也评估了其表达。通过心肌梗死（myocardial infarction，MI）诱导心力衰竭（n = 10）；将结果与假手术组（n = 10）进行比较。通过超声心动图评估心室功能。通过实时 PCR 分析基因表达，通过 Western blot 分析腓肠肌和比目鱼肌中的蛋白水平；通过形态计量学分析评估纤维营养。MI 组出现胸腔积液和右心室肥厚等心力衰竭证据。MI 组观察到左心室扩张和功能障碍。在比目鱼肌中，横截面积（P = 0.006）和卵泡抑素蛋白水平（Sham 为 1.00 +/- 0.36；MI 为 0.18 +/- 0.06 任意单位；P = 0.03）均降低，且 MI 组卵泡抑素基因表达呈降低趋势（P = 0.085）。两组间肌肉生长抑制素表达无变化。在腓肠肌中，MI 组的所有参数均与 Sham 相似。总之，我们的数据表明，在慢性心力衰竭期间，骨骼肌营养减少与肌肉生长抑制素不变和卵泡抑素表达减少有关。
