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Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle
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Transcriptional deficits in oxidative phosphorylation with statin myopathy

Monica J Hubal1, Kimberly A Reich, Andrea De Biase

  • 1Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.

Muscle & Nerve
|October 15, 2011
PubMed
Abstract

Insights

Statin therapy can cause muscle problems, especially with strenuous exercise. Pre-existing energy production deficits in skeletal muscle may increase the risk of statin myopathy, impacting gene expression related to cellular energy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Exercise Physiology

Background:

  • Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are common hyperlipidemia drugs.
  • Statin use can lead to skeletal muscle toxicity (statin myopathy).
  • The molecular mechanisms underlying statin myopathy remain unclear.

Purpose of the Study:

  • To investigate the effects of statin treatment and eccentric exercise on gene expression.
  • To compare transcriptional patterns in statin-myopathic versus statin-tolerant individuals.

Main Methods:

  • Skeletal muscle biopsies were obtained from statin-myopathic (Sym) and statin-tolerant (Asym) subjects.
  • Biopsies were collected post-exercise (concentric and eccentric) at baseline and after statin treatment.
  • Transcriptional patterns were analyzed to identify differences between groups.

Main Results:

  • Statin-myopathic individuals showed reduced gene expression for oxidative phosphorylation and mitochondrial ribosomal proteins.
  • These differences were observed both before and after statin treatment combined with eccentric exercise.
  • Eccentric exercise exacerbated the observed gene expression differences.

Conclusions:

  • Pre-existing deficiencies in skeletal muscle energy production may predispose individuals to statin myopathy.
  • Impaired mitochondrial function could be a key factor in statin-induced muscle symptoms.
  • Eccentric exercise may trigger or worsen statin myopathy in susceptible individuals.

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