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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. -- Highlights: ► The most common and problematic side effect of statins is myopathy. ► Patients treated with statins showed impairment of mitochondrial respiration. ► Statins-treated patients showed altered frequency and amplitude of calcium sparks.

Authors:
 [1];  [2];  [3]; ;  [1];  [2];  [4]; ; ;  [1];  [2]
  1. U1046, INSERM, Université Montpellier 1 and Université Montpellier 2, 34295 Montpellier (France)
  2. (France)
  3. (AME2P), BP 80026, F-63171 Aubière cedex (France)
  4. CHRU Montpellier, 34295 Montpellier (France)
Publication Date:
OSTI Identifier:
22215262
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 259; Journal Issue: 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CALCIUM; CREATINE; HEART; LIPOPROTEINS; MITOCHONDRIA; MUSCLES; PAIN; PATIENTS; RATS; RESPIRATION; SARCOPLASMIC RETICULUM

Citation Formats

Sirvent, P., E-mail: pascal.sirvent@univ-bpclermont.fr, CHRU Montpellier, 34295 Montpellier, Clermont Université, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques, Fabre, O., Bordenave, S., CHRU Montpellier, 34295 Montpellier, Hillaire-Buys, D., Raynaud De Mauverger, E., Lacampagne, A., Mercier, J., and CHRU Montpellier, 34295 Montpellier. Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2012.01.008.
Sirvent, P., E-mail: pascal.sirvent@univ-bpclermont.fr, CHRU Montpellier, 34295 Montpellier, Clermont Université, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques, Fabre, O., Bordenave, S., CHRU Montpellier, 34295 Montpellier, Hillaire-Buys, D., Raynaud De Mauverger, E., Lacampagne, A., Mercier, J., & CHRU Montpellier, 34295 Montpellier. Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins. United States. doi:10.1016/J.TAAP.2012.01.008.
Sirvent, P., E-mail: pascal.sirvent@univ-bpclermont.fr, CHRU Montpellier, 34295 Montpellier, Clermont Université, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques, Fabre, O., Bordenave, S., CHRU Montpellier, 34295 Montpellier, Hillaire-Buys, D., Raynaud De Mauverger, E., Lacampagne, A., Mercier, J., and CHRU Montpellier, 34295 Montpellier. Thu . "Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins". United States. doi:10.1016/J.TAAP.2012.01.008.
@article{osti_22215262,
title = {Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins},
author = {Sirvent, P., E-mail: pascal.sirvent@univ-bpclermont.fr and CHRU Montpellier, 34295 Montpellier and Clermont Université, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques and Fabre, O. and Bordenave, S. and CHRU Montpellier, 34295 Montpellier and Hillaire-Buys, D. and Raynaud De Mauverger, E. and Lacampagne, A. and Mercier, J. and CHRU Montpellier, 34295 Montpellier},
abstractNote = {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. -- Highlights: ► The most common and problematic side effect of statins is myopathy. ► Patients treated with statins showed impairment of mitochondrial respiration. ► Statins-treated patients showed altered frequency and amplitude of calcium sparks.},
doi = {10.1016/J.TAAP.2012.01.008},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 259,
place = {United States},
year = {Thu Mar 01 00:00:00 EST 2012},
month = {Thu Mar 01 00:00:00 EST 2012}
}