The effects of statins on mitochondrial function

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dc.contributor.advisorNeufer, P. Darrellen_US
dc.contributor.authorMayo, William Josephen_US
dc.contributor.departmentExercise and Sports Scienceen_US
dc.date.accessioned2013-08-24T18:29:11Z
dc.date.available2013-08-24T18:29:11Z
dc.date.issued2013en_US
dc.description.abstractStatins, or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are among the most commonly prescribed medications in the United States. They are commonly used to treat hypercholesterolemia, a condition in which blood cholesterol is elevated above normal levels. Statins serve as an effective means of lowering blood cholesterol, which is associated with a decreased risk for cardiovascular disease. Patients diagnosed with or at risk of coronary artery disease are therefore commonly prescribed statins in order to prevent the development of plaque induced narrowing of coronary arteries. While well tolerated by most patients, reports indicate that approximately 10.5% of patients suffer from statin induced myopathies. Commonly reported side effects include muscular cramps, stiffness, heaviness, weakness, tendonitis, and decreased power during physical activity. Reports have also emerged of statin induced changes in the function of skeletal muscle mitochondria. These reports provided the impetus for an examination of the possibility that statin induced mitochondrial abnormalities play a role in the etiology of the myopathies reported by patients. This study was therefore designed to test the hypothesis that statins interfere with normal mitochondrial function. Specifically, the purpose was to determine whether seven days of in vivo administration of simvastatin or atorvastatin reduces mitochondrial respiratory capacity, decreases mitochondrial calcium retention capacity, and/or increases mitochondrial H₂O₂ emission potential. Twelve female subjects participated in this study. Subjects underwent a 7-day treatment with either 40-mg simvastatin or 80-mg atorvastatin, administered orally. Muscle biopsies were obtained from the rectus femoris muscle at four time points: pre-/post-statin consumption on day one of the study, and pre-/post-statin consumption one week later. Skeletal muscle samples were permeabilized and measurements of mitochondrial respiratory capacity, calcium retention capacity, and H₂O₂ emission potential were performed. The results of this study provide little evidence to support the hypothesis that statins administered in vivo over the course of a seven day treatment interfere with normal mitochondrial function. No significant treatment effect emerged either acutely (2-3 hours following statin treatment) or chronically (after a seven day treatment). Statins seemed to have little to no effect on mitochondrial respiratory capacity, calcium retention capacity, and H₂O₂ emission potential during the seven day treatment. The results of this study suggest that the deleterious effects of statin exposure reported in the literature are not a consequence of acute or short term (7d) changes in mitochondrial function with commencement of statin therapy. However, in vitro studies demonstrate that acute statin exposure can indeed negatively affect mitochondrial respiratory capacity, calcium retention capacity, and H₂O₂ emission potential (C-T Lin & PD Neufer, unpublished data). Further studies will be required to elucidate the exact nature of statin induced mitochondrial abnormalities in humans and their role in the etiology of statin induced myopathies.en_US
dc.description.degreeM.S.en_US
dc.format.extent68 p.en_US
dc.format.mediumdissertations, academicen_US
dc.identifier.urihttp://hdl.handle.net/10342/4201
dc.language.isoen_US
dc.publisherEast Carolina Universityen_US
dc.subjectPhysiologyen_US
dc.subjectH₂O₂en_US
dc.subjectMitochondriaen_US
dc.subjectMyopathyen_US
dc.subjectRespiratory capacityen_US
dc.subjectSkeletal muscleen_US
dc.subjectBiology, Physiology
dc.subject.lcshStatins (Cardiovascular agents)
dc.subject.lcshMitochondrial pathology
dc.titleThe effects of statins on mitochondrial functionen_US
dc.typeMaster's Thesisen_US

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