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Coenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance.
MedLine Citation:
PMID:  22653988     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background: Statins are cholesterol-lowering drugs widely used in the prevention of cardiovascular diseases; however, they are associated with various types of myopathies. Statins inhibit HMG-CoA reductase and thus decrease biosynthesis of low-density lipoprotein cholesterol and may also reduce ubiquinones, essential coenzymes of a mitochondrial electron transport chain, which contain isoprenoid residues, synthesized through an HMG-CoA reductase-dependent pathway. Therefore, we hypothesized that statin treatment might influence physical performance through muscular mitochondrial dysfunction due to ubiquinone deficiency. Methods and Results: The effect of two statins, atorvastatin and pravastatin, on ubiquinone content, mitochondrial function and physical performance was examined by using statin-treated mice. Changes in energy metabolism in association with statin-treatment were studied by using cultured myocytes. We found that atorvastatin-treated mice developed muscular mitochondrial dysfunction due to ubiquinone deficiency and a decrease in exercise endurance without affecting muscle mass and strength. Meanwhile, pravastatin at ten times higher dose of atorvastatin had no such effects. In cultured myocytes, atorvastatin-related decrease in mitochondrial activity led to a decrease in oxygen utilization and an increase in lactate production. Conversely, coenzyme Q(10) treatment in atorvastatin-treated mice reversed atorvastatin-related mitochondrial dysfunction and a decrease in oxygen utilization, and thus improved exercise endurance. Conclusion: Atorvastatin decreased exercise endurance in mice through mitochondrial dysfunction due to ubiquinone deficiency. Ubiquinone supplementation with coenzyme Q(10) could reverse atorvastatin-related mitochondrial dysfunction and decrease in exercise tolerance.
Authors:
Ayako Muraki; Kazutoshi Miyashita; Masanori Mitsuishi; Masanori Tamaki; Kumiko Tanaka; Hiroshi Itoh
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-31
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  -     ISSN:  1522-1601     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-6-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Keio University.
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