The impact of physical activity on statin-associated skeletal muscle myopathy

BACKGROUND: HMG-CoA reductase inhibitors (statins) are a common and effective pharmacological means of treating hypercholesterolemia and decreasing cardiovascular risk. The most common side effect of statins is skeletal muscle myopathy, which appears to be exacerbated by exercise. PURPOSE: The purpose of this study was to examine the effects of statin treatment with novel or accustomed exercise in hypercholesterolemic (ApoE-/-) or wild type (WT) mice on muscle function (grip strength, isometric force, and daily activity level), markers of mitochondrial content (mtDNA and PGC1-α), skeletal muscle oxidative stress (4HNE), and protein degradation (atrogin-1). METHODS: Mice were divided into three different activity groups, sedentary (Sed), novel (Nov), accustomed (Acct) (n=60). Mice in all groups received daily injections of either simvastatin (20mg/kg) or saline for the later 2 weeks with (Acct)/without (Nov) the prior 2 weeks of wheel running (WR). Daily WR distance was recorded. At 4 weeks, plantarflexor isometric force and grip strength were measured. mtDNA, 4HNE, and atrogin-1 and PGC1-α were measured as markers of mitochondrial content by real time PCR, ELISA, real time RT-PCR, respectively. RESULTS: Two weeks of statin treatment decreased running wheel activity, isometric force, and grip strength regardless of exercise groups. In saline-injected animals, both Nov and Acct EX increased mitochondrial content and PGC1-α levels, but this effect was blunted by statins. There was an interaction effect on muscle 4HNE, and atrogin-1 gene expression between statins and EX. Specifically, there was an overall trend for a decrease in these markers when statins were provided to sedentary mice, though both novel and accustomed exercise increased their levels. CONCLUSION: These results indicate that statin treatment had a negative impact on muscle function and cellular regulation in muscles in hypercholesterolemic mice. The combination of exercise and statin treatment decreased mitochondrial content and the expression of PGC1-α. Additionally, muscle oxidative stress and the protein degradation were increased by the combination of exercise and statins while exercise alone elicited mitochondrial and antioxidant benefits.

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

2015

Author dc:creator

• Chung, Hae Ryong

Contributors dc:contributor

• Wilund, Kenneth
• Woods, Jeffrey A.
• Boppart, Marni
• Haus, Jacob

• Statin
• Cholesterol
• Exercise
• Muscle myopathy

Statement dc:rights

• Copyright 2014 Hae Ryong Chung

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/72929

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/72929