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The role of mitochondria in statin-induced myopathy.
Eur J Clin Invest. 2015 Jul; 45(7):745-54.EJ

Abstract

BACKGROUND

Statins inhibit hydroxymethylglutaryl-coenzyme A reductase, decrease plasma low-density lipoprotein cholesterol and reduce cardiovascular morbidity and mortality. They can also exert adverse effects, mostly affecting skeletal muscle, ranging from mild myalgia to rhabdomyolysis.

MATERIALS AND METHODS

Based on a PubMed search until December 2014, this review summarizes studies on statin effects on muscle mitochondrial morphology and function in the context of myopathy.

RESULTS

Possible mechanisms of statin-induced myopathy include lower cholesterol synthesis and production of prenylated proteins, reduced dolichols and increased atrogin-1 expression. Statin-treated patients frequently feature decreased muscle coenzyme Q10 (CoQ10) contents, suggesting that statins might impair mitochondrial function. In cell cultures, statins diminish muscle oxygen consumption, promote mitochondrial permeability transient pore opening and generate apoptotic proteins. Animal models confirm the statin-induced decrease in muscle CoQ10, but reveal no changes in mitochondrial enzyme activities. Human studies yield contradictory results, with decreased CoQ10, elevated lipids, decreased enzyme activities in muscle and impaired maximal oxygen uptake in several but not all studies. Some patients are susceptible to statin-induced myopathy due to variations in genes encoding proteins involved in statin uptake and biotransformation such as the solute carrier organic anion transporter family member 1B1 (SLCO1B1) or cytochrome P450 (CYP2D6, CYP3A4, CYP3A5). Carriers for carnitine palmitoyltransferase II deficiency and McArdle disease also present with higher prevalence of statin-induced myopathy.

CONCLUSIONS

Despite the widespread use of statins, the pathogenesis of statin-induced myopathy remains unclear, requiring prospective randomized controlled trials with intensive phenotyping also for identifying strategies for its risk assessment, prevention and treatment.

Authors+Show Affiliations

Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany. German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany.Dipartimento di Scienze Farmacologiche e Biomolecolari (DISFeB), Università degli Studi di Milano, Milan, Italy. IRCCS Multimedica, Milan, Italy.Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany. German Center for Diabetes Research (DZD e.V.), Düsseldorf, Germany. Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

25991405

Citation

Apostolopoulou, Maria, et al. "The Role of Mitochondria in Statin-induced Myopathy." European Journal of Clinical Investigation, vol. 45, no. 7, 2015, pp. 745-54.
Apostolopoulou M, Corsini A, Roden M. The role of mitochondria in statin-induced myopathy. Eur J Clin Invest. 2015;45(7):745-54.
Apostolopoulou, M., Corsini, A., & Roden, M. (2015). The role of mitochondria in statin-induced myopathy. European Journal of Clinical Investigation, 45(7), 745-54. https://doi.org/10.1111/eci.12461
Apostolopoulou M, Corsini A, Roden M. The Role of Mitochondria in Statin-induced Myopathy. Eur J Clin Invest. 2015;45(7):745-54. PubMed PMID: 25991405.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of mitochondria in statin-induced myopathy. AU - Apostolopoulou,Maria, AU - Corsini,Alberto, AU - Roden,Michael, Y1 - 2015/06/15/ PY - 2015/01/30/received PY - 2015/05/13/accepted PY - 2015/5/21/entrez PY - 2015/5/21/pubmed PY - 2016/3/29/medline KW - Mitochondria KW - myopathy KW - skeletal muscle KW - statins KW - ubiquinone SP - 745 EP - 54 JF - European journal of clinical investigation JO - Eur. J. Clin. Invest. VL - 45 IS - 7 N2 - BACKGROUND: Statins inhibit hydroxymethylglutaryl-coenzyme A reductase, decrease plasma low-density lipoprotein cholesterol and reduce cardiovascular morbidity and mortality. They can also exert adverse effects, mostly affecting skeletal muscle, ranging from mild myalgia to rhabdomyolysis. MATERIALS AND METHODS: Based on a PubMed search until December 2014, this review summarizes studies on statin effects on muscle mitochondrial morphology and function in the context of myopathy. RESULTS: Possible mechanisms of statin-induced myopathy include lower cholesterol synthesis and production of prenylated proteins, reduced dolichols and increased atrogin-1 expression. Statin-treated patients frequently feature decreased muscle coenzyme Q10 (CoQ10) contents, suggesting that statins might impair mitochondrial function. In cell cultures, statins diminish muscle oxygen consumption, promote mitochondrial permeability transient pore opening and generate apoptotic proteins. Animal models confirm the statin-induced decrease in muscle CoQ10, but reveal no changes in mitochondrial enzyme activities. Human studies yield contradictory results, with decreased CoQ10, elevated lipids, decreased enzyme activities in muscle and impaired maximal oxygen uptake in several but not all studies. Some patients are susceptible to statin-induced myopathy due to variations in genes encoding proteins involved in statin uptake and biotransformation such as the solute carrier organic anion transporter family member 1B1 (SLCO1B1) or cytochrome P450 (CYP2D6, CYP3A4, CYP3A5). Carriers for carnitine palmitoyltransferase II deficiency and McArdle disease also present with higher prevalence of statin-induced myopathy. CONCLUSIONS: Despite the widespread use of statins, the pathogenesis of statin-induced myopathy remains unclear, requiring prospective randomized controlled trials with intensive phenotyping also for identifying strategies for its risk assessment, prevention and treatment. SN - 1365-2362 UR - https://www.unboundmedicine.com/medline/citation/25991405/The_role_of_mitochondria_in_statin_induced_myopathy_ L2 - https://doi.org/10.1111/eci.12461 DB - PRIME DP - Unbound Medicine ER -