title: The Impact of Exercise on Statin-Associated Skeletal Muscle Myopathy.
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.
authors.affiliation: Renal and Cardiovascular Disease Research Laboratory, Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Hae R
authors.initials: HR
authors.lastname: Chung
authors.affiliation: Renal and Cardiovascular Disease Research Laboratory, Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Mayand
authors.initials: M
authors.lastname: Vakil
authors.affiliation: Molecular Muscle Physiology Laboratory, Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.|Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Munroe
authors.affiliation: Molecular Muscle Physiology Laboratory, Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.|Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Alay
authors.initials: A
authors.lastname: Parikh
authors.affiliation: Renal and Cardiovascular Disease Research Laboratory, Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Meador
authors.affiliation: Renal and Cardiovascular Disease Research Laboratory, Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Pei T
authors.initials: PT
authors.lastname: Wu
authors.affiliation: Renal and Cardiovascular Disease Research Laboratory, Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Jin H
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Exercise Immunology Research Laboratory, Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Woods
authors.affiliation: Renal and Cardiovascular Disease Research Laboratory, Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Wilund
authors.affiliation: Molecular Muscle Physiology Laboratory, Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.|Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Marni D
authors.initials: MD
authors.lastname: Boppart
mesh_terms: D000818:Animals; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D051379:Mice; D018482:Muscle, Skeletal / Q000473:pathology*; D009135:Muscular Diseases / Q000139:chemically induced*; D009929:Organ Size; D010805:Physical Conditioning, Animal
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol