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

Statin;Cholesterol;Exercise;Muscle myopathy

Chung, Hae Ryong

关键词: Statin;    Cholesterol;    Exercise;    Muscle myopathy;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/72929/Hae%20Ryong_Chung.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

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.