科研之友
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摘要
Background: In the failing human heart, abnormalities of Ca2+ cycling have been described, but there is scant knowledge about Ca2+ handling in the skeletal muscle of humans with heart failure (HF). We tested the hypothesis that in humans with HF, Ca2+ cycling proteins in skeletal muscle are abnormal. %26lt;br%26gt;Methods and Results: 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 Ca2+-ATPase (SERCA)2a, which is responsible for Ca2+ sequestration into the sarcoplasmic reticulum(SR), was lower in HE versus controls (4.8 +/- 0.5 vs 7.5 +/- 0.8 AU, P = .01). Although phospholamban (PLN), which inhibits SERCA2a, was not different in HE 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 Ca2+ 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. %26lt;br%26gt;Conclusion: In chronic HF, marked abnormalities of Ca2+ 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 Ca2+-calmodulin-dependent-protein kinase II. (J Cardiac Fail 2012;18:724-733)
- 出版日期2012-9
