UCLA Department of Medicine, Los Angeles, CA, USA.
J Card Fail. 2012 Sep;18(9):724-33. doi: 10.1016/j.cardfail.2012.07.005.
In the failing human heart, abnormalities of Ca(2+) cycling have been described, but there is scant knowledge about Ca(2+) handling in the skeletal muscle of humans with heart failure (HF). We tested the hypothesis that in humans with HF, Ca(2+) cycling proteins in skeletal muscle are abnormal.
Ten advanced HF patients (50.4 ± 3.7 years), and 9 age-matched controls underwent vastus lateralis biopsy. Western blot analysis showed that sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)2a, which is responsible for Ca(2+) sequestration into the sarcoplasmic reticulum(SR), was lower in HF versus controls (4.8 ± 0.5 vs 7.5 ± 0.8 AU, P = .01). Although phospholamban (PLN), which inhibits SERCA2a, was not different in HF versus controls, phosphorylation (SER16 site) of PLN, which relieves this inhibition, was reduced (0.8 ± 0.1 vs 3.9 ± 0.9 AU, P = .004). Dihydropyridine receptors were reduced in HF, (2.1 ± 0.4 vs 3.6 ± 0.5 AU, P = .04). We tested the hypothesis that these abnormalities of Ca(2+) handling protein content and regulation were due to increased oxidative stress, but oxygen radical scavenger proteins were not elevated in the skeletal muscle of HF patients.
In chronic HF, marked abnormalities of Ca(2+) handling proteins are present in skeletal muscle, which mirror those in failing heart tissue. This suggests a common mechanism, such as chronic augmentation of sympathetic activity and autophosphorylation of Ca(2+)-calmodulin-dependent-protein kinase II.
在衰竭的人心肌中，已经描述了 Ca（2+）循环的异常，但对于心力衰竭（HF）患者骨骼肌中的 Ca（2+）处理知之甚少。我们检验了这样一个假设，即在 HF 患者中，骨骼肌中的 Ca（2+）循环蛋白异常。
10 名晚期 HF 患者（50.4±3.7 岁）和 9 名年龄匹配的对照者接受了股外侧肌活检。Western blot 分析显示，肌浆网（内质网）Ca（2+）-ATP 酶（SERCA）2a 负责将 Ca（2+）摄取到肌浆网（SR）中，在 HF 患者中低于对照组（4.8±0.5 vs 7.5±0.8 AU，P=0.01）。尽管 PLN（抑制 SERCA2a）在 HF 患者中与对照组没有差异，但 PLN 的磷酸化（SER16 位）减轻了这种抑制，（0.8±0.1 vs 3.9±0.9 AU，P=0.004）。二氢吡啶受体在 HF 中减少，（2.1±0.4 vs 3.6±0.5 AU，P=0.04）。我们检验了这样一个假设，即 Ca（2+）处理蛋白含量和调节的这些异常是由于氧化应激增加所致，但 HF 患者骨骼肌中的氧自由基清除蛋白并未升高。
在慢性 HF 中，骨骼肌中存在明显的 Ca（2+）处理蛋白异常，这与衰竭心脏组织中的异常相似。这表明存在共同的机制，如慢性增强交感神经活性和 Ca（2+）-钙调蛋白依赖性蛋白激酶 II 的自磷酸化。
