Oxidative phenotype protects myofibers from pathological insults induced by chronic heart failure in mice
Oxidative phenotype protects myofibers from pathological insults induced by chronic heart failure in mice
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DOI：
10.2353/ajpath.2007.060505
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发表时间：
2007-02-01
影响因子：
6
通讯作者：
Yan, Zhen
中科院分区：
文献类型：
--
作者：
Li, Ping;Waters, Richard E.;Yan, Zhen
慢性心力衰竭（CHF）骨骼肌异常的纤维特异性尚未确定。我们发现转基因小鼠（8周龄）与心脏特异性过表达的钙螯合蛋白发展的CRF（肺短轴缩短率降低50.9%，肺重量增加56.4%，P < 0.001），恶病质（体重下降37.8%，P < 0.001）和运动不耐受（运动至力竭距离减少69.3%，P < 0.001），而肌纤维类型组成没有显著变化。慢氧化比目鱼肌维持肌肉质量，而快速糖酵解胫骨前肌和跖肌发生萎缩（分别为11.6%和13.3%; P < 0.05）。在跖肌中，糖酵解型IId/x和IIb纤维的横截面积显著减少（20.3%，P < 0.05），而氧化型I和IIa纤维的横截面积无显著减少（P> 0.05）。快速糖酵解的白色股外侧肌。肌节变性，细胞色素c氧化酶IV（39.5%，P < 0.01）和过氧化物酶体增殖物激活受体辅激活因子1 α蛋白表达下降（30.3%，P < 0.01），同时MAFbx/Atrogin-1 mRNA显著诱导沿着。这些研究结果表明，运动不耐症可以发生在CHF没有纤维类型转换的骨骼肌和氧化表型，使肌纤维耐病理性损伤引起的CHF。
The fiber specificity of skeletal muscle abnormalities in chronic heart failure (CHF) has not been defined. We show here that transgenic mice (8 weeks old) with cardiac-specific overexpression of calsequestrin developed CRF (50.9% decrease in fractional shortening and 56.4% increase hi lung weight, P < 0.001), cachexia (37.8% decrease in body weight, P < 0.001), and exercise intolerance (69.3% decrease in running distance to exhaustion, P < 0.001) without a significant change in muscle fiber-type composition. Slow oxidative soleus muscle maintained muscle mass, whereas fast glycolytic tibialis anterior and plantaris muscles underwent atrophy (11.6 and 13.3%, respectively; P < 0.05). in plantaris muscle, glycolytic type IId/x and IIb, but not oxidative type I and IIa, fibers displayed significant decreases in cross-sectional area (20.3%, P < 0.05). Fast glycolytic white vastus lateralis muscle. showed sarcomere degeneration and decreased cytochrome c oxidase IV (39.5%, P < 0.01) and peroxisome proliferator-activated receptory coactivator 1 alpha protein expression (30.3%, P < 0.01) along with a dramatic induction of the MAFbx/Atrogin-1 mRNA. These findings suggest that exercise intolerance can occur in CHF without fiber type switching in skeletal muscle and that oxidative phenotype renders myofibers resistant to pathological insults induced by CHF.