title: Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins.
abstract: 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.
authors.affiliation: Université Montpellier 1 & Université Montpellier, Montpellier, France. pascal.sirvent@univ-bpclermont.fr
authors.forename: P
authors.initials: P
authors.lastname: Sirvent
authors.forename: O
authors.initials: O
authors.lastname: Fabre
authors.forename: S
authors.initials: S
authors.lastname: Bordenave
authors.forename: D
authors.initials: D
authors.lastname: Hillaire-Buys
authors.forename: E
authors.initials: E
authors.lastname: Raynaud De Mauverger
authors.forename: A
authors.initials: A
authors.lastname: Lacampagne
authors.forename: J
authors.initials: J
authors.lastname: Mercier
mesh_terms: D000328:Adult; D001706:Biopsy; D020013:Calcium Signaling / Q000187:drug effects*; D003402:Creatine Kinase / Q000378:metabolism; D015444:Exercise / Q000502:physiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase