Some molecular mechanisms of the statin-associated myopathy development




statins, atherosclerosis, myopathy, rhabdomyolysis, ubiquinone, apoptosis


Topicality. Statins are the most commonly prescribed lipid-lowering drugs. It is proven that their administration significantly reduces the risk of cardiovascular complications. However, along with high efficiency, they provoke the development of side effects on the muscular system – myopathies and rhabdomyolysis. Mechanisms of myotoxity formation currently remains a controversial issue.

Aim. To summarize the existing literature data concerning the molecular mechanisms underlying the development of myopathy associated with statins treatment.

Results and discussion. According to modern concepts, molecular mechanisms of myopathy and rhabdomyolysis during treatment with statins may be associated with apoptosis of muscle fibers (as a result of violations of proteins post-translational modification); has an autoimmune nature (through its impact on major histocompatibility complex); lesion of ubiquitin-proteasome system; due to deficiency of ubiquinone and carnitine, and decreased synthesis of endogenous cholesterol.

Conclusions. Molecular mechanisms of statin-associated myopathy development are complex and have both idiopathic and genetically nature.


Toth, P. P., Harper, C. R., Jacobson, T. A. (2008). Clinical characterization and molecular mechanisms of statin myopathy. Expert Review of Cardiovascular Therapy, 6 (7), 955–969. doi: 10.1586/14779072.6.7.955

Mohassel, P., Mammen, A. L. (2013). The spectrum of statin myopathy. Current Opinion in Rheumatology, 25 (6), 747–752. doi: 10.1097/01.bor.0000434673.85515.89

Harper, C. R., Jacobson, T. A. (2007). The broad spectrum of statin myopathy: from myalgia to rhabdomyolysis. Current Opinion in Lipidology, 18 (4), 401–408. doi: 10.1097/mol.0b013e32825a6773

Tomaszewski, M., Stępień, K. M., Tomaszewska, J., Czuczwar, S. J. (2011). Statin–induced myopathies. Pharmacological Reports, 63 (4), 859–866. doi: 10.1016/s1734–1140(11)70601–6

Vaklavas, C., Chatzizisis, Y. S., Ziakas, A., Zamboulis, C., Giannoglou, G. D. (2009). Molecular basis of statin–associated myopathy. Atherosclerosis, 202 (1), 18–28. doi: 10.1016/j.atherosclerosis.2008.05.021

Owczarek, J., Jasiñska, M., Orszulak–Michalak, D. (2005). Drug–induced myopathies. An overview of the possible mechanisms. Pharmacol Rep., 57, 23–34.

Moßhammer, D., Schaeffeler, E., Schwab, M., Mörike, K. (2014). Mechanisms and assessment of statin–related muscular adverse effects. British Journal of Clinical Pharmacology, 78 (3), 454–466. doi: 10.1111/bcp.12360

Keen, H. I., Krishnarajah, J., Bates, T. R., Watts, G. F. (2014). Statin myopathy: the fly in the ointment for the prevention of cardiovascular disease in the 21st century? Expert Opinion on Drug Safety, 13 (9), 1227–1239. doi: 10.1517/14740338.2014.937422

Rosenson, R. S. (2004). Current overview of statin–induced myopathy. The American Journal of Medicine, 116 (6), 408–416. doi: 10.1016/j.amjmed.2003.10.033

Phillips, P. S., Haas, R. H. (2008). Statin myopathy as a metabolic muscle disease. Expert Review of Cardiovascular Therapy, 6 (7), 971–978. doi: 10.1586/14779072.6.7.971

Taylor, B. A., Thompson, P. D. (2015). Muscle–related side–effects of statins. Current Opinion in Lipidology, 26 (3), 221–227. doi: 10.1097/mol.0000000000000174

Sirvent, P., Mercier, J., Lacampagne, A. (2008). New insights into mechanisms of statin–associated myotoxicity. Current Opinion in Pharmacology, 8 (3), 333–338. doi: 10.1016/j.coph.2007.12.010

Vrablik, M., Zlatohlavek, L., Stulc, T. et al. (2014). Statin–associated myopathy: from genetic predisposition to clinical management. Physiological research, 63, S327.

Ruaño, G., Windemuth, A., Wu, A. H. B., Kane, J. P., Malloy, M. J., Pullinger, C. R., Thompson, P. D. (2011). Mechanisms of statin–induced myalgia assessed by physiogenomic associations. Atherosclerosis, 218 (2), 451–456. doi: 10.1016/j.atherosclerosis.2011.07.007

Taylor, B. A., Lorson, L., White, C. M., Thompson, P. D. (2015). A randomized trial of coenzyme Q10 in patients with confirmed Statin Myopathy. Atherosclerosis, 238 (2), 329–335. doi: 10.1016/j.atherosclerosis.2014.12.016

Apostolopoulou, M., Corsini, A., Roden, M. (2015). The role of mitochondria in statin–induced myopathy. European Journal of Clinical Investigation, 45 (7), 745–754. doi: 10.1111/eci.12461

Deichmann, R., Lavie, C., Asher, T. et al. (2015). The interaction between statins and exercise: mechanisms and strategies to counter the musculoskeletal side effects of this combination therapy. The Ochsner Journal, 15, 429–437.

Du Souich, P., Roederer, G., Dufour, R. (2017). Myotoxicity of statins: Mechanism of action. Pharmacology & Therapeutics. doi: 10.1016/j.pharmthera.2017.02.029

Ghatak, A., Faheem, O., Thompson, P. D. (2010). The genetics of statin–induced myopathy. Atherosclerosis, 210 (2), 337–343. doi: 10.1016/j.atherosclerosis.2009.11.033

Needham, M., Mastaglia, F. L. (2014). Statin myotoxicity: A review of genetic susceptibility factors. Neuromuscular Disorders, 24 (1), 4–15. doi: 10.1016/j.nmd.2013.09.011

Lotteau, S., Colyer, J., Hopkins, P. Steele, D. (2016). Statins induce post–translational modification of RyR1 in human and rodent skeletal muscle: a mechanism for myopathy. The Physiological Society, 2016.

Lawrence, J., Moyer, C., Ameri, M. et al. (2014). Statin–Induced Myopathy is Mediated by Isoprenoid Depletion and is Independent of Serum Cholesterol Levels. Circulation, 130, С. A13907–A13907.

Muntean, D. M., Thompson, P. D., Catapano, A. L., Stasiolek, M., Fabis, J., Muntner, P., Banach, M. (2017). Statin–associated myopathy and the quest for biomarkers: can we effectively predict statin–associated muscle symptoms? Drug Discovery Today, 22 (1), 85–96. doi: 10.1016/j.drudis.2016.09.001Schirris

Schirris, T. J. J., Renkema, G. H., Ritschel, T., Voermans, N. C., Bilos, A., van Engelen, B. G. M., Russel, F. G. M. (2015). Statin–Induced Myopathy Is Associated with Mitochondrial Complex III Inhibition. Cell Metabolism, 22 (3), 399–407. doi: 10.1016/j.cmet.2015.08.002

Schaefer, J., Jackson, S. (2016). Statin Myopathy. Acquired Neuromuscular Disorders, 113–122. doi: 10.1007/978–3–319–29514–5_8





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