Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, UNESP, Brazil.
Int J Cardiol. 2013 Aug 10;167(3):698-703. doi: 10.1016/j.ijcard.2012.03.063. Epub 2012 Mar 30.
Although skeletal muscle atrophy and changes in myosin heavy chain (MyHC) isoforms have often been observed during heart failure, their pathophysiological mechanisms are not completely defined. In this study we tested the hypothesis that skeletal muscle phenotype changes are related to myogenic regulatory factors and myostatin/follistatin expression in spontaneously hypertensive rats (SHR) with heart failure.
After developing tachypnea, SHR were subjected to transthoracic echocardiogram. Pathological evidence of heart failure was assessed during euthanasia. Age-matched Wistar-Kyoto (WKY) rats were used as controls. Soleus muscle morphometry was analyzed in histological sections, and MyHC isoforms evaluated by electrophoresis. Protein levels were assessed by Western blotting.
Student'st test and Pearson correlation.
All SHR presented right ventricular hypertrophy and seven had pleuropericardial effusion. Echocardiographic evaluation showed dilation in the left chambers and left ventricular hypertrophy with systolic and diastolic dysfunction in SHR. Soleus weight and fiber cross sectional areas were lower (WKY 3615 ± 412; SHR 2035 ± 224 μm(2); P<0.001), and collagen fractional volume was higher in SHR. The relative amount of type I MyHC isoform was increased in SHR. Myogenin, myostatin, and follistatin expression was lower and MRF4 levels higher in SHR. Myogenin and follistatin expression positively correlated with fiber cross sectional areas and MRF4 levels positively correlated with I MyHC isoform.
Reduced myogenin and follistatin expression seems to participate in muscle atrophy while increased MRF4 protein levels can modulate myosin heavy chain isoform shift in skeletal muscle of spontaneously hypertensive rats with heart failure.
尽管心力衰竭时经常观察到骨骼肌萎缩和肌球蛋白重链（MyHC）同工型的变化，但它们的病理生理机制尚不完全明确。在这项研究中，我们检验了这样一个假设，即骨骼肌表型的变化与自发性高血压大鼠（SHR）心力衰竭中的成肌调节因子和肌抑素/激活素的表达有关。
在出现呼吸急促后，对 SHR 进行了经胸超声心动图检查。在安乐死期间评估心力衰竭的病理证据。将年龄匹配的 Wistar-Kyoto（WKY）大鼠用作对照。在组织学切片中分析比目鱼肌形态计量学，并通过电泳评估 MyHC 同工型。通过 Western 印迹法评估蛋白水平。
Student's t 检验和 Pearson 相关性。
所有 SHR 均出现右心室肥厚，7 只出现胸膜心包积液。超声心动图评估显示 SHR 的左心室扩张和左心室肥厚，伴有收缩和舒张功能障碍。比目鱼肌重量和纤维横截面积较低（WKY 3615±412；SHR 2035±224μm²；P<0.001），而 SHR 的胶原分数较高。SHR 的 I 型 MyHC 同工型相对含量增加。成肌因子、肌抑素和激活素的表达降低，而 MRF4 水平升高。成肌因子和激活素的表达与纤维横截面积呈正相关，而 MRF4 水平与 I 型 MyHC 同工型呈正相关。
成肌因子和激活素表达的减少似乎参与了肌肉萎缩，而 MRF4 蛋白水平的增加可以调节心力衰竭的自发性高血压大鼠骨骼肌中肌球蛋白重链同工型的转变。
