Transcriptional deficits in oxidative phosphorylation with statin myopathy

Muscle Nerve. 2011 Sep;44(3):393-401. doi: 10.1002/mus.22081.


Introduction: 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy
  • Cross-Over Studies
  • Energy Metabolism / genetics
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperlipidemias / drug therapy
  • Male
  • Middle Aged
  • Muscle Proteins / genetics*
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscular Diseases / chemically induced*
  • Muscular Diseases / metabolism*
  • Muscular Diseases / physiopathology
  • Oligonucleotide Array Sequence Analysis
  • Oxidative Phosphorylation*
  • Signal Transduction / genetics
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / physiology*


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Muscle Proteins