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Influence of statins on distinct circulating microRNAs during prolonged aerobic exercise

 Pil-Ki Min  ;  Joseph Park  ;  Stephanie Isaacs  ;  Beth A. Taylor  ;  Paul D. Thompson  ;  Chris Troyanos  ;  Pierre D’Hemecourt  ;  Sophia Dyer  ;  Stephen Y. Chan  ;  Aaron L. Baggish 
 JOURNAL OF APPLIED PHYSIOLOGY , Vol.120(6) : 711-720, 2016 
Journal Title
Issue Date
Animals ; Biomarkers/blood ; Biomarkers/metabolism ; Cells, Cultured ; Exercise/physiology* ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology* ; Male ; Mice ; MicroRNAs/blood* ; Middle Aged ; Muscle Contraction/drug effects ; Muscle Contraction/physiology ; Muscle Fibers, Skeletal/drug effects ; Muscle Fibers, Skeletal/metabolism ; Muscle Fibers, Skeletal/physiology ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/physiology ; Muscular Diseases/blood ; Muscular Diseases/metabolism ; Physical Endurance/drug effects* ; Physical Endurance/physiology ; Running/physiology
exercise ; hydroxymethylglutaryl-CoA reductase inhibitors ; microRNAs ; muscle contraction ; skeletal muscle
Statins exacerbate exercise-induced skeletal muscle injury. Muscle-specific microRNAs (myomiRs) increase in plasma after prolonged exercise, but the patterns of myomiRs release after statin-associated muscle injury have not been examined. We examined the relationships between statin exposure, in vitro and in vivo muscle contraction, and expression of candidate circulating myomiRs. We measured plasma levels of myomiRs, circulating microRNA-1 (c-miR-1), c-miR-133a, c-miR-206, and c-miR-499-5p from 28 statin-using and 28 nonstatin-using runners before (PRE), immediately after (FINISH), and 24 h after they ran a 42-km footrace (the 2011 Boston marathon) (POST-24). To examine these cellular-regulation myomiRs, we used contracting mouse C2C12 myotubes in culture with and without statin exposure to compare intracellular and extracellular expression of these molecules. In marathoners, c-miR-1, c-miR-133a, and c-miR-206 increased at FINISH, returned to baseline at POST-24, and were unaffected by statin use. In contrast, c-miR-499-5p was unchanged at FINISH but increased at POST-24 among statin users compared with PRE and runners who did not take statins. In cultured C2C12 myotubes, extracellular c-miR-1, c-miR-133a, and c-miR-206 were significantly increased by muscle contraction regardless of statin use. In contrast, extracellular miR-499-5p was unaffected by either isolated statin exposure or isolated carbachol exposure but it was increased when muscle contraction was combined with statin exposure. In summary, we found that statin-potentiated muscle injury during exercise is accompanied by augmented extracellular release of miR-499-5p. Thus c-miR-499-5p may serve as a biomarker of statin-potentiated muscle damage.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Min, Pil Ki(민필기) ORCID logo https://orcid.org/0000-0001-7033-7651
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