title: Abnormalities of calcium handling proteins in skeletal muscle mirror those of the heart in humans with heart failure: a shared mechanism?
abstract: BACKGROUND
  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.
  
  
  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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: UCLA Department of Medicine, Los Angeles, CA, USA. hmiddlekauff@mednet.ucla.edu
authors.forename: Holly R
authors.initials: HR
authors.lastname: Middlekauff
authors.forename: Chris
authors.initials: C
authors.lastname: Vigna
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Verity
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Horwich
authors.forename: Michele A
authors.initials: MA
authors.lastname: Hamilton
authors.forename: Perry
authors.initials: P
authors.lastname: Shieh
authors.forename: A Russell
authors.initials: AR
authors.lastname: Tupling
mesh_terms: D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism*; D016022:Case-Control Studies; D017079:Exercise Tolerance; D005260:Female; D006321:Heart; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D015398:Signal Transduction; D013223:Statistics as Topic; D013564:Sympathetic Nervous System; D055815:Young Adult
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium