title: Transcriptional deficits in oxidative phosphorylation with statin myopathy.
abstract: BACKGROUND
  Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, are widely used drugs for hyperlipidemia and are generally well-tolerated, but the can produce skeletal muscle toxicity. The molecular mechanisms driving statin myopathy are unknown. We investigated the effects of statin treatment and eccentric (damaging) exercise on transcriptional patterns between statin myopathy (Sym; N = 9) and statin-tolerant subjects (Asym; N = 6).
  
  
  METHODS
  Skeletal muscle biopsies were collected 6 h post-exercise at baseline and after statin treatment. Subjects performed concentric (non-damaging) exercise with one leg and concentric + eccentric exercise with the other leg using a cross-over design between time-points.
  
  
  RESULTS
  Sym as compared with Asym demonstrated decreased skeletal muscle gene expression for oxidative phosphorylation-related and mitochondrial ribosomal protein genes before and after statin treatment with eccentric exercise.
  
  
  CONCLUSIONS
  These results suggest that pre-existing deficiencies in energy production may contribute to the development of symptoms during statin therapy, especially when muscle is exposed to eccentric exercise.
authors: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
authors: Monica J
authors: MJ
authors: Hubal
authors: Kimberly A
authors: KA
authors: Reich
authors: Andrea
authors: A
authors: De Biase
authors: Cherie
authors: C
authors: Bilbie
authors: Priscilla M
authors: PM
authors: Clarkson
authors: Eric P
authors: EP
authors: Hoffman
authors: Paul D
authors: PD
authors: Thompson
mesh_terms: D000328:Adult; D001706:Biopsy; D018592:Cross-Over Studies; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009124:Muscle Proteins