The impact of exercise on statin-associated skeletal muscle myopathy

Hae R. Chung, Mayand Vakil, Michael Munroe, Alay Parikh, Benjamin M. Meador, Pei T. Wu, Jin H. Jeong, Jeffrey A. Woods, Kenneth R. Wilund, Marni D. Boppart

Research output: Contribution to journalArticle

Abstract

HMG-CoA reductase inhibitors (statins) are the most effective pharmacological means of reducing cardiovascular disease risk. The most common side effect of statin use is skeletal muscle myopathy, which may be exacerbated by exercise. Hypercholesterolemia and training status are factors that are rarely considered in the progression of myopathy. The purpose of this study was to determine the extent to which acute and chronic exercise can influence statin-induced myopathy in hypercholesterolemic (ApoE-/- ) mice. Mice either received daily injections of saline or simvastatin (20 mg/kg) while: 1) remaining sedentary (Sed), 2) engaging in daily exercise for two weeks (novel, Nov), or 3) engaging in daily exercise for two weeks after a brief period of training (accustomed, Acct) (2x3 design, n = 60). Cholesterol, activity, strength, and indices of myofiber damage and atrophy were assessed. Running wheel activity declined in both exercise groups receiving statins (statin x time interaction, p<0.05). Cholesterol, grip strength, and maximal isometric force were significantly lower in all groups following statin treatment (statin main effect, p<0.05). Mitochondrial content and myofiber size were increased and 4-HNE was decreased by exercise (statin x exercise interaction, p<0.05), and these beneficial effects were abrogated by statin treatment. Exercise (Acct and Nov) increased atrogin-1 mRNA in combination with statin treatment, yet enhanced fiber damage or atrophy was not observed. The results from this study suggest that exercise (Nov, Acct) does not exacerbate statin-induced myopathy in ApoE-/- mice, yet statin treatment reduces activity in a manner that prevents muscle from mounting a beneficial adaptive response to training.

Original languageEnglish (US)
Article numbere0168065
JournalPloS one
Volume11
Issue number12
DOIs
StatePublished - Dec 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Chung, H. R., Vakil, M., Munroe, M., Parikh, A., Meador, B. M., Wu, P. T., Jeong, J. H., Woods, J. A., Wilund, K. R., & Boppart, M. D. (2016). The impact of exercise on statin-associated skeletal muscle myopathy. PloS one, 11(12), [e0168065]. https://doi.org/10.1371/journal.pone.0168065