Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 259, Issue 2, Pages 263-268Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2012.01.008
Keywords
Skeletal muscle; Sta tins; Calcium homeostasis; Mitochondria; Muscle pain
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Funding
- agence francaise de securite sanitaire des produits de sante (AFSSAPS)
- institut national de la sante et de la recherche medicale (INSERM)
- association francaise contre les myopathies (AFM)
- fondation pour la recherche medicale (FRM)
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The most common and problematic side effect of statins is myopathy. To date, the patho-physiological mechanisms of statin myotoxicity are still not clearly understood. In previous studies, we showed that acute application in vitro of simvastatin caused impairment of mitochondrial function and dysfunction of calcium homeostasis in human and rat healthy muscle samples. We thus evaluated in the present study, mitochondrial function and calcium signaling in muscles of patients treated with statins, who present or not muscle symptoms, by oxygraphy and recording of calcium sparks, respectively. Patients treated with statins showed impairment of mitochondrial respiration that involved mainly the complex I of the respiratory chain and altered frequency and amplitude of calcium sparks. The muscle problems observed in statin-treated patients appear thus to be related to impairment of mitochondrial function and muscle calcium homeostasis. confirming the results we previously reported in vitro. (C) 2012 Elsevier Inc. All rights reserved.
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