Statin-associated skeletal muscle damage and its interactions with novel or accustomed exercise

Statin drugs are a very commonly prescribed medication, and their most common side effect is some degree of skeletal muscle myopathy. Unfortunately, this side effect is more likely/severe in statin users who are also exercisers. Purpose: To examine the previously unaddressed interactions of statin treatment with novel vs. accustomed exercise, as well as to examine cellular markers of the stress response—heat shock proteins (Hsps)—and apoptosis—activated caspases. Methods: C57 mice were treated with daily cerivastatin (1/mg/kg/day) or saline for two weeks, with/without concomitant wheel running (RW) (Novel & Sedentary groups). Additional groups also performed two weeks of RW activity prior to the initiation of statin treatment (Accustomed groups). RW activity was tracked daily, and hindlimb plantarflexor maximal force and fatigue was measured at the end of the intervention. Hsp25, αB-Crystallin, Caspase-3, and Caspase-9 were measured by western blot, plasma creatine kinase (CK) was assessed by activity assay. Results: Statin treatment did not significantly impact RW activity, however both sedentary and novel-exercise groups showed decrements in muscle force and fatigability with statin treatment. The effect on maximal force was more severe in the novel-exercise group, while accustomed exercise mice were protected from this decrement. Plasma creatine kinase levels did not correlate with functional outcomes. No significant effect of statin treatment was found for hsp25 or αB-Crystallin expression, though both proteins were increased by both the novel and accustomed exercise interventions. A significant injection by activity interaction was found for active caspase-9 expression, with statins increasing expression in the sedentary and novel groups, but decreasing expression in the accustomed groups. Active caspase-3 was not detectable in any group. Conclusions: These results indicate that exercise training prior to statin treatment can protect against myopathy, rather than exacerbate it, as seen with novel exercise. Additionally, accustomed exercise was able to reverse statin treatment’s activation of caspase-9, though the physiological significance of this is unclear, as the lack of caspase-3 expression indicates that apoptosis did not in fact occur. An upregulation in Hsp expression with exercise may have contributed to the preservation of muscle force and decreased caspase-9 expression in the accustomed groups.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Kinesiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Meador, Benjamin M.

Contributors dc:contributor

• Huey, Kimberly A.
• Evans, Ellen M.
• Fernhall, Bo
• Boppart, Marni D.
• Johnson, Rodney W.

• Statins
• Myopathy
• Exercise
• Muscle Function
• Heat Shock Proteins
• Caspase

Statement dc:rights

• Copyright 2010 Benjamin M. Meador. Some sections copyright John Wiley & Sons (reprint permission has been obtained)

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/18603

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/18603