Myotoxicity of statins: Mechanism of action

Pharmacology and Therapeutics

Volumn 175, Issue , 2017, Pages 1-16

  du Souich, Patrick ^a,b   Roederer, Ghislaine ^b   Dufour, Robert ^a,b  

^a UNIVERSITÉ DE MONTRÉAL   (Canada)

^b CLIN RESEARCH INSTITUTE OF MONTREAL   (Canada)

Author keywords

Chloride channels; Lactate; Mechanism of action; Mitochondria; Muscle remodeling; Statins myopathy

Indexed keywords

3 HYDROXY METHYLGLUTARYL COENZYME A REDUCTASE; BREAST CANCER RESISTANCE PROTEIN; CALCIUM ION; CHLORIDE; CREATINE KINASE; CYTOCHROME P450; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE ACTIVATOR; ISOPROTEIN; LACTIC ACID; MULTIDRUG RESISTANCE PROTEIN; MULTIDRUG RESISTANCE PROTEIN 1; REACTIVE OXYGEN METABOLITE; SOLUTE CARRIER ORGANIC ANION TRANSPORTER 1B1; UBIQUINONE; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG;

APOPTOSIS; DRUG ACCUMULATION; DRUG EFFECT; ENERGY RESOURCE; FEMALE; HUMAN; LIVER; METABOLISM; MITOCHONDRIAL DNA DEPLETION; MOUSE; MUSCLE; MUSCLE CELL; MUSCLE DISEASE; MUSCLE FATIGUE; MUSCLE FUNCTION; MYALGIA; NONHUMAN; PHARMACOKINETICS; PHYSIOLOGY; PRIORITY JOURNAL; PROPHYLAXIS; PROTEIN DEGRADATION; RAT; RESPIRATORY CHAIN; REVIEW; SARCOPLASM; SKELETAL MUSCLE; STATIN INDUCED MYOTOXICITY; THERAPY; ANIMAL; CHEMICALLY INDUCED; PATHOPHYSIOLOGY;

ANIMALS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MUSCLE CELLS; MUSCULAR DISEASES;

EID: 85013196981     PISSN: 01637258     EISSN: 1879016X     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2017.02.029     Document Type: Review

References (213)

1. Akimoto, T., Pohnert, S.C., Li, P., Zhang, M., Gumbs, C., Rosenberg, P.B., et al. Exercise stimulates Pgc-1alpha transcription in skeletal muscle through activation of the p38 MAPK pathway. The Journal of Biological Chemistry 280 (2005), 19587–19593.
2. Alfirevic, A., Neely, D., Armitage, J., Chinoy, H., Cooper, R.G., Laaksonen, R., et al. Phenotype standardization for statin-induced myotoxicity. Clinical Pharmacology and Therapeutics 96 (2014), 470–476.
3. Allen, D.G., Lamb, G.D., Westerblad, H., Skeletal muscle fatigue: Cellular mechanisms. Physiological Reviews 88 (2008), 287–332.
4. Banach, M., Serban, C., Sahebkar, A., Ursoniu, S., Rysz, J., Muntner, P., et al. Effects of coenzyme Q10 on statin-induced myopathy: A meta-analysis of randomized controlled trials. Mayo Clinic Proceedings 90 (2015), 24–34.
5. Banach, M., Serban, C., Ursoniu, S., Rysz, J., Muntner, P., Toth, P.P., et al. Statin therapy and plasma coenzyme Q10 concentrations—A systematic review and meta-analysis of placebo-controlled trials. Pharmacological Research 99 (2015), 329–336.
6. Banerjee, N., Fonge, H., Mikhail, A., Reilly, R.M., Bendayan, R., Allen, C., Estrone-3-sulphate, a potential novel ligand for targeting breast cancers. PLoS One, 8, 2013, e64069.
7. Becker, M.L., Elens, L.L., Visser, L.E., Hofman, A., Uitterlinden, A.G., van Schaik, R.H., Stricker, B.H., Genetic variation in the ABCC2 gene is associated with dose decreases or switches to other cholesterol-lowering drugs during simvastatin and atorvastatin therapy. The Pharmacogenomics Journal 13 (2013), 251–256.
8. Benton, C.R., Nickerson, J.G., Lally, J., Han, X.X., Holloway, G.P., Glatz, J.F., et al. Modest PGC-1alpha overexpression in muscle in vivo is sufficient to increase insulin sensitivity and palmitate oxidation in subsarcolemmal, not intermyofibrillar, mitochondria. The Journal of Biological Chemistry 283 (2008), 4228–4240.
9. Benton, C.R., Yoshida, Y., Lally, J., Han, X.X., Hatta, H., Bonen, A., PGC-1alpha increases skeletal muscle lactate uptake by increasing the expression of MCT1 but not MCT2 or MCT4. Physiological Genomics 35 (2008), 45–54.
10. Benton, C.R., Campbell, S.E., Tonouchi, M., Hatta, H., Bonen, A., Monocarboxylate transporters in subsarcolemmal and intermyofibrillar mitochondria. Biochemical and Biophysical Research Communications 323 (2004), 249–253.
11. Birmingham, B.K., Bujac, S.R., Elsby, R., Azumaya, C.T., Wei, C., Chen, Y., et al. Impact of ABCG2 and SLCO1B1 polymorphisms on pharmacokinetics of rosuvastatin, atorvastatin and simvastatin acid in Caucasian and Asian subjects: a class effect?. European Journal of Clinical Pharmacology 71 (2015), 341–355.
12. Bonen, A., The expression of lactate transporters (MCT1 and MCT4) in heart and muscle. European Journal of Applied Physiology 86 (2001), 6–11.
13. Bonifacio, A., Mullen, P.J., Mityko, I.S., Navegantes, L.C., Bouitbir, J., Krähenbühl, S., Simvastatin induces mitochondrial dysfunction and increased atrogin-1 expression in H9c2 cardiomyocytes and mice in vivo. Archives of Toxicology 90 (2016), 203–215.
14. Bonifacio, A., Sanvee, G.M., Bouitbir, J., Krähenbühl, S., The AKT/mTOR signaling pathway plays a key role in statin-induced myotoxicity. Biochimica et Biophysica Acta-Molecular Cell Research 1853 (2015), 1841–1849.
15. Bonifacio, A., Sanvee, G.M., Brecht, K., Kratschmar, D.V., Odermatt, A., Bouitbir, J., Krähenbühl, S., IGF-1 prevents simvastatin-induced myotoxicity in C2C12 myotubes. Archives of Toxicology, 2016, Oct 12 (Epub ahead of print).
16. Bosgra, S., van de Steeg, E., Vlaming, M.L., Verhoeckx, K.C., Huisman, M.T., Verwei, M., Wortelboer, H.M., Predicting carrier-mediated hepatic disposition of rosuvastatin in man by scaling from individual transfected cell-lines in vitro using absolute transporter protein quantification and PBPK modeling. European Journal of Pharmaceutical Sciences 65 (2014), 156–166.
17. Bouitbir, J., Charles, A.L., Echaniz-Laguna, A., Kindo, M., Daussin, F., Auwerx, J., et al. Opposite effects of statins on mitochondria of cardiac and skeletal muscles: A ‘mitohormesis’ mechanism involving reactive oxygen species and PGC-1. European Heart Journal 33 (2012), 1397–1407.
18. Bouitbir, J., Singh, F., Charles, A.L., Schlagowski, A.I., Bonifacio, A., Echaniz-Laguna, A., et al. Statins trigger mitochondrial reactive oxygen species-induced apoptosis in glycolytic skeletal muscle. Antioxidants & Redox Signaling 24 (2016), 84–98.
19. Brinton, E.A., Maki, K.C., Jacobson, T.A., Sponseller, C.A., Cohen, J.D., Metabolic syndrome is associated with muscle symptoms among statin users. Journal of Clinical Lipidology 10 (2016), 1022–1029.
20. Brown, A.J., Ikonen, E., Olkkonen, V.M., Cholesterol precursors: More than mere markers of biosynthesis. Current Opinion in Lipidology 25 (2014), 133–139.
21. Brunham, L.R., Lansberg, P.J., Zhang, L., Miao, F., Carter, C., Hovingh, G.K., et al. Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin. The Pharmacogenomics Journal 12 (2012), 233–237.
22. Buitrago, C., Pardo, V.G., Boland, R., Role of VDR in 1α,25-dihydroxyvitamin D3-dependent non-genomic activation of MAPKs, Src and Akt in skeletal muscle cells. The Journal of Steroid Biochemistry and Molecular Biology 136 (2013), 125–130.
23. Burckhardt, G., Burckhardt, B.C., In vitro and in vivo evidence of the importance of organic anion transporters (OATs) in drug therapy. Handbook of Experimental Pharmacology 201 (2011), 29–104.
24. Camerino, G.M., De Bellis, M., Conte, E., Liantonio, A., Musaraj, K., Cannone, M., et al. Statin-induced myotoxicity is exacerbated by aging: A biophysical and molecular biology study in rats treated with atorvastatin. Toxicology and Applied Pharmacology 306 (2016), 36–46.
25. Canestaro, W.J., Austin, M.A., Thummel, K.E., Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review. Genetics in Medicine 16 (2014), 810–819.
26. Cao, P., Hanai, J., Tanksale, P., Imamura, S., Sukhatme, V.P., Lecker, S.H., Statin-induced muscle damage and atrogin-1 induction is the result of a geranylgeranylation defect. The FASEB Journal 23 (2009), 2844–2854.
27. Carr, D.F., O'Meara, H., Jorgensen, A.L., Campbell, J., Hobbs, M., McCann, G., et al. SLCO1B1 genetic variant associated with statin-induced myopathy: Proof-of-concept study using the clinical practice research datalink. Clinical Pharmacology and Therapeutics 94 (2013), 695–701.
28. Causevic-Ramosevac, A., Semiz, S., Drug interactions with statins. Acta Pharmaceutica 63 (2013), 277–293.
29. Chasman, D.I., Giulianini, F., MacFadyen, J., Barratt, B.J., Nyberg, F., Ridker, P.M., Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction: The justification for the use of statins in prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Circulation. Cardiovascular Genetics 5 (2012), 257–264.
30. Chauvin, B., Drouot, S., Barrail-Tran, A., Taburet, A.M., Drug-drug interactions between HMG-CoA reductase inhibitors (statins) and antiviral protease inhibitors. Clinical Pharmacokinetics 52 (2013), 815–831.
31. Choi, H.C., Song, P., Xie, Z., Wu, Y., Xu, J., Zhang, M., et al. Reactive nitrogen species is required for the activation of the AMP-activated protein kinase by statin in vivo. The Journal of Biological Chemistry 283 (2008), 20186–20197.
32. Clavel, S., Siffroi-Fernandez, S., Coldefy, A.S., Boulukos, K., Pisani, D.F., Dérijard, B., Regulation of the intracellular localization of Foxo3a by stress-activated protein kinase signaling pathways in skeletal muscle cells. Molecular and Cellular Biology 30 (2010), 470–480.
33. Cohen, J.D., Brinton, E.A., Ito, M.K., Jacobson, T.A., Understanding Statin Use in America and Gaps in Patient Education (USAGE): An internet-based survey of 10,138 current and former statin users. Journal of Clinical Lipidology 6 (2012), 208–215.
34. Copaja, M., Venegas, D., Aránguiz, P., Canales, J., Vivar, R., Catalán, M., et al. Simvastatin induces apoptosis by a Rho-dependent mechanism in cultured cardiac fibroblasts and myofibroblasts. Toxicology and Applied Pharmacology 255 (2011), 57–64.
35. Coupel, S., Leboeuf, F., Boulday, G., Soulillou, J.P., Charreau, B., RhoA activation mediates phosphatidylinositol 3-kinase-dependent proliferation of human vascular endothelial cells: An alloimmune mechanism of chronic allograft nephropathy. Journal of the American Society of Nephrology 15 (2004), 2429–2439.
36. Cunningham, J.T., Rodgers, J.T., Arlow, D.H., Vazquez, F., Mootha, V.K., Puigserver, P., mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature 450 (2007), 736–740.
37. Dai, R., Feng, J., Wang, Y., Yang, Y., Deng, C., Tang, X., et al. Association between SLCO1B1 521 T > C and 388 A > G polymorphisms and statins effectiveness: A meta-analysis. Journal of Atherosclerosis and Thrombosis 22 (2015), 796–815.
38. Danik, J.S., Chasman, D.I., MacFadyen, J.G., Nyberg, F., Barratt, B.J., Ridker, P.M., Lack of association between SLCO1B1 polymorphisms and clinical myalgia following rosuvastatin therapy. American Heart Journal 165 (2013), 1008–1014.
39. de Keyser, C.E., Peters, B.J., Becker, M.L., Visser, L.E., Uitterlinden, A.G., Klungel, O.H., et al. The SLCO1B1 c.521T > C polymorphism is associated with dose decrease or switching during statin therapy in the Rotterdam Study. Pharmacogenetics and Genomics 24 (2014), 43–51.
40. Donnelly, L.A., Doney, A.S., Tavendale, R., Lang, C.C., Pearson, E.R., Colhoun, H.M., et al. Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: A go-DARTS study. Clinical Pharmacology and Therapeutics 89 (2011), 210–216.
41. Draeger, A., Monastyrskaya, K., Mohaupt, M., Hoppeler, H., Savolainen, H., Allemann, C., Babiychuk, E.B., Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia. The Journal of Pathology 210 (2006), 94–102.
42. Egan, B., Carson, B.P., Garcia-Roves, P.M., Chibalin, A.V., Sarsfield, F.M., Barron, N., et al. Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor coactivator-1 mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle. The Journal of Physiology 588 (2010), 1779–1790.
43. El-Ganainy, S.O., El-Mallah, A., Abdallah, D., Khattab, M.M., Mohy El-Din, M.M., El-Khatib, A.S., Elucidation of the mechanism of atorvastatin-induced myopathy in a rat model. Toxicology 359-360 (2016), 29–38.
44. Ferrari, M., Guasti, L., Maresca, A., Mirabile, M., Contini, S., Grandi, A.M., et al. Association between statin-induced creatine kinase elevation and genetic polymorphisms in SLCO1B1, ABCB1 and ABCG2. European Journal of Clinical Pharmacology 70 (2014), 539–547.
45. Fiegenbaum, M., da Silveira, F.R., Van der Sand, C.R., Van der Sand, L.C., Ferreira, M.E., Pires, R.C., Hutz, M.H., The role of common variants of ABCB1, CYP3A4, and CYP3A5 genes in lipid-lowering efficacy and safety of simvastatin treatment. Clinical Pharmacology and Therapeutics 78 (2005), 551–558.
46. Fitzgerald, K., White, S., Borodovsky, A., Bettencourt, B.R., Strahs, A., Clausen, V., et al. A highly durable RNAi therapeutic inhibitor of PCSK9. The New England Journal of Medicine 376 (2017), 41–51.
47. Flint, O.P., Masters, B.A., Gregg, R.E., Durham, S.K., HMG CoA reductase inhibitor-induced myotoxicity: pravastatin and lovastatin inhibit the geranylgeranylation of low-molecular-weight proteins in neonatal rat muscle cell culture. Toxicology and Applied Pharmacology 145 (1997), 99–110.
48. Fujino, H., Saito, T., Ogawa, S., Kojima, J., Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. The Journal of Pharmacy and Pharmacology 57 (2005), 1305–1311.
49. Galtier, F., Mura, T., Raynaud de Mauverger, E., Chevassus, H., Farret, A., Gagnol, J.P., et al. Effect of a high dose of simvastatin on muscle mitochondrial metabolism and calcium signaling in healthy volunteers. Toxicology and Applied Pharmacology 263 (2012), 281–286.
50. Gee, R.H., Spinks, J.N., Malia, J.M., Johnston, J.D., Plant, N.J., Plant, K.E., Inhibition of prenyltransferase activity by statins in both liver and muscle cell lines is not causative of cytotoxicity. Toxicology 329 (2015), 40–48.
51. 2 +-dependent regulations and signaling in skeletal muscle: From electro-mechanical coupling to adaptation. International Journal of Molecular Sciences 16 (2015), 1066–1095.
52. Generaux, G.T., Bonomo, F.M., Johnson, M., Doan, K.M., Impact of SLCO1B1 (OATP1B1) and ABCG2 (BCRP) genetic polymorphisms and inhibition on LDL-C lowering and myopathy of statins. Xenobiotica 41 (2011), 639–651.
53. Giacomini, K.M., Balimane, P.V., Cho, S.K., Eadon, M., Edeki, T., Hillgren, K.M., et al. International transporter consortium commentary on clinically important transporter polymorphisms. Clinical Pharmacology and Therapeutics 94 (2013), 23–26.
54. Girgis, C.M., Cha, K.M., Houweling, P.J., Rao, R., Mokbe, N., Lin, M., et al. Vitamin D receptor ablation and vitamin D deficiency result in reduced grip strength, altered muscle fibers, and increased myostatin in mice. Calcified Tissue International 97 (2015), 602–610.
55. Girgis, C.M., Clifton-Bligh, R.J., Hamrick, M.W., Holick, M.F., Gunton, J.E., The roles of vitamin D in skeletal muscle: Form, function, and metabolism. Endocrine Reviews 34 (2013), 33–83.
56. Gluba-Brzozka, A., Franczyk, B., Toth, P.P., Rysz, J., Banach, M., Molecular mechanisms of statin intolerance. Archives of Medical Science 12 (2016), 645–658.
57. Gomez-Cabrera, M.C., Salvador-Pascual, A., Cabo, H., Ferrando, B., Viña, J., Redox modulation of mitochondriogenesis in exercise. Does antioxidant supplementation blunt the benefits of exercise training?. Free Radical Biology & Medicine 86 (2015), 37–46.
58. Grassi, B., Rossiter, H.B., Zoladz, J.A., Skeletal muscle fatigue and decreased efficiency: Two sides of the same coin?. Exercise and Sport Sciences Reviews 43 (2015), 75–83.
59. Graven-Nielsen, T., Mense, S., The peripheral apparatus of muscle pain: Evidence from animal and human studies. The Clinical Journal of Pain 17 (2001), 2–10.
60. Greer, E.L., Oskoui, P.R., Banko, M.R., Maniar, J.M., Gygi, M.P., Gygi, S.P., Brunet, A., The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor. The Journal of Biological Chemistry 282 (2007), 30107–30119.
61. Gu, Q., Paulose-Ram, R., Burt, V.L., Kit, B.K., Prescription cholesterol-lowering medication use in adults aged 40 and over: United States, 2003–2012. NCHS Data Brief 177 (2014), 1–8.
62. Guijarro, C., Blanco-Colio, L.M., Ortego, M., Alonso, C., Ortiz, A., Plaza, J.J., et al. 3-Hydroxy-3-methylglutaryl coenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture. Circulation Research 83 (1998), 490–500.
63. Guyton, J.R., Bays, H.E., Grundy, S.M., Jacobson, T.A., The National Lipid Association Statin Intolerance Panel, An assessment by the statin intolerance panel: 2014 update. Journal of Clinical Lipidology 8:3 Suppl (2014), S72–S81.
64. Halestrap, A.P., Wilson, M.C., The monocarboxylate transporter family—role and regulation. IUBMB Life 64 (2012), 109–119.
65. Hanai, J., Cao, P., Tanksale, P., Imamura, S., Koshimizu, E., Zhao, J., et al. The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. The Journal of Clinical Investigation 117 (2007), 3940–3951.
66. Handschin, C., Regulation of skeletal muscle cell plasticity by the peroxisome proliferator-activated receptor γ coactivator 1α. Journal of Receptor and Signal Transduction Research 30 (2010), 376–384.
67. Handy, D.E., Loscalzo, J., Redox regulation of mitochondrial function. Antioxidants & Redox Signaling 16 (2012), 1323–1367.
68. Hardie, D.G., Sakamoto, K., AMPK: A key sensor of fuel and energy status in skeletal muscle. Physiology (Bethesda) 21 (2006), 48–60.
69. Hashimoto, T., Hussien, R., Oommen, S., Gohil, K., Brooks, G.A., Lactate sensitive transcription factor network in L6 cells: Activation of MCT1 and mitochondrial biogenesis. The FASEB Journal 21 (2007), 2602–2612.
70. Hashimoto, T., Brooks, G.A., Mitochondrial lactate oxidation complex and an adaptive role for lactate production. Med. Sci. Sports Exerc 40 (2008), 486–494.
71. Hermann, M., Bogsrud, M.P., Molden, E., Asberg, A., Mohebi, B.U., Ose, L., Retterstøl, K., Exposure of atorvastatin is unchanged but lactone and acid metabolites are increased several-fold in patients with atorvastatin-induced myopathy. Clinical Pharmacology and Therapeutics 79 (2006), 532–539.
72. Ho, R.H., Tirona, R.G., Leake, B.F., Glaeser, H., Lee, W., Lemke, C.J., et al. Drug and bile acid transporters in rosuvastatin hepatic uptake: Function, expression, and pharmacogenetics. Gastroenterology 130 (2006), 1793–1806.
73. Hoenig, M.R., Walker, P.J., Gurnsey, C., Beadle, K., Johnson, L., The C3435T polymorphism in ABCB1 influences atorvastatin efficacy and muscle symptoms in a high-risk vascular cohort. Journal of Clinical Lipidology 5 (2011), 91–96.
74. Hoppeler, H., Molecular networks in skeletal muscle plasticity. The Journal of Experimental Biology 219 (2016), 205–213.
75. Horscroft, J.A., Murray, A.J., Skeletal muscle energy metabolism in environmental hypoxia: Climbing towards consensus. Extreme Physiology & Medicine, 3, 2014, 19.
76. Hou, Q., Li, S., Li, L., Li, Y., Sun, X., Tian, H., Association between SLCO1B1 Gene T521C polymorphism and statin-related myopathy risk: A meta-analysis of case-control studies. Medicine (Baltimore), 94, 2015, e1268.
77. Hovingh, G.K., Ray, K.K., Boekholdt, S.M., Is cholesteryl ester transfer protein inhibition an effective strategy to reduce cardiovascular risk? CETP as a target to lower CVD risk: Suspension of disbelief?. Circulation 132 (2015), 433–440.
78. Huang, Y., Chen, J.B., Yang, B., Shen, H., Liang, J.J., Luo, Q., RhoA/ROCK pathway regulates hypoxia-induced myocardial cell apoptosis. Asian Pacific Journal of Tropical Medicine 7 (2014), 884–888.
79. Ieiri, I., Suwannakul, S., Maeda, K., Uchimaru, H., Hashimoto, K., Kimura, M., et al. SLCO1B1 (OATP1B1, an uptake transporter) and ABCG2 (BCRP, an efflux transporter) variant alleles and pharmacokinetics of pitavastatin in healthy volunteers. Clinical Pharmacology and Therapeutics 82 (2007), 541–547.
80. Imbrici, P., Altamura, C., Pessia, M., Mantegazza, R., Desaphy, J.F., Camerino, D.C., ClC-1 chloride channels: State-of-the-art research and future challenges. Frontiers in Cellular Neuroscience, 9, 2015, 156.
81. Irrcher, I., Ljubicic, V., Hood, D.A., Interactions between ROS and AMP kinase activity in the regulation of PGC-1alpha transcription in skeletal muscle cells. American Journal of Physiology. Cell Physiology 296 (2009), C116–C123.
82. Jäger, S., Handschin, C., St-Pierre, J., Spiegelman, B.M., AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proceedings of the National Academy of Sciences of the United States of America 104 (2007), 12017–12022.
83. 2 levels cause skeletal muscle atrophy via AMP-activated kinase (AMPK), FoxO3a protein, and muscle-specific ring finger protein 1 (MuRF1). The Journal of Biological Chemistry 290 (2015), 9183–9194.
84. Jetty, V., Glueck, C.J., Wang, P., Shah, P., Prince, M., Lee, K., et al. Safety of 50,000–100,000 units of vitamin D3/week in vitamin D-deficient, hypercholesterolemic patients with reversible statin intolerance. North American Journal of Medical Sciences 8 (2016), 156–162.
85. Jiang, J., Tang, Q., Feng, J., Dai, R., Wang, Y., Yang, Y., et al. Association between SLCO1B1 − 521T > C and − 388A > G polymorphisms and risk of statin-induced adverse drug reactions: A meta-analysis. SpringerPlus, 5, 2016, 1368.
86. Johnson, T.E., Zhang, X., Bleicher, K.B., Dysart, G., Loughlin, A.F., Schaefer, W.H., Umbenhauer, D.R., Statins induce apoptosis in rat and human myotube cultures by inhibiting protein geranylgeranylation but not ubiquinone. Toxicology and Applied Pharmacology 200 (2004), 237–250.
87. Joncquel-Chevalier Curt, M., Voicu, P.M., Fontaine, M., Dessein, A.F., Porchet, N., Mention-Mulliez, K., et al. Creatine biosynthesis and transport in health and disease. Biochimie 119 (2015), 146–165.
88. Karalis, D.G., Wild, R.A., Maki, K.C., Gaskins, R., Jacobson, T.A., Sponseller, C.A., Cohen, J.D., Gender differences in side effects and attitudes regarding statin use in the Understanding Statin Use in America and Gaps in Patient Education (USAGE) study. Journal of Clinical Lipidology 10 (2016), 833–841.
89. Kaufmann, P., Török, M., Zahno, A., Waldhauser, K.M., Brecht, K., Krähenbühl, S., Toxicity of statins on rat skeletal muscle mitochondria. Cellular and Molecular Life Sciences 63 (2006), 2415–2425.
90. Kazior, Z., Willis, S.J., Moberg, M., Apró, W., Calbet, J.A., Holmberg, H.C., Blomstrand, E., endurance exercise enhances the effect of strength training on muscle fiber size and protein expression of Akt and mTOR. PLoS One, 11, 2016, e0149082.
91. Keppler, D., Multidrug resistance proteins (MRPs, ABCCs): Importance for pathophysiology and drug therapy. Handbook of Experimental Pharmacology 201 (2011), 299–323.
92. Keskitalo, J.E., Pasanen, M.K., Neuvonen, P.J., Niemi, M., Different effects of the ABCG2 c.421C > A SNP on the pharmacokinetics of fluvastatin, pravastatin and simvastatin. Pharmacogenomics 10 (2009), 1617–1624.
93. Keskitalo, J.E., Zolk, O., Fromm, M.F., Kurkinen, K.J., Neuvonen, P.J., Niemi, M., ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin and rosuvastatin. Clinical Pharmacology and Therapeutics 86 (2009), 197–203.
94. Keskitalo, J.E., Kurkinen, K.J., Neuvonen, M., Backman, J.T., Neuvonen, P.J., Niemi, M., No significant effect of ABCB1 haplotypes on the pharmacokinetics of fluvastatin, pravastatin, lovastatin, and rosuvastatin. British Journal of Clinical Pharmacology 68 (2009), 207–213.
95. Keskitalo, J.E., Kurkinen, K.J., Neuvonen, P.J., Niemi, M., ABCB1 haplotypes differentially affect the pharmacokinetics of the acid and lactone forms of simvastatin and atorvastatin. Clinical Pharmacology and Therapeutics 84 (2008), 457–461.
96. Khayznikov, M., Hemachrandra, K., Pandit, R., Kumar, A., Wang, P., Glueck, C.J., Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation. North American Journal of Medical Sciences 7 (2015), 86–93.
97. Kikutani, Y., Kobayashi, M., Konishi, T., Sasaki, S., Narumi, K., Furugen, A., et al. Involvement of monocarboxylate transporter 4 expression in statin-induced cytotoxicity. Journal of Pharmaceutical Sciences 105 (2016), 1544–1549.
98. Kim, D., Chung, J., Akt: Versatile mediator of cell survival and beyond. Journal of Biochemistry and Molecular Biology 35 (2002), 106–115.
99. Kimchi-Sarfaty, C., Oh, J.M., Kim, I.W., Sauna, Z.E., Calcagno, A.M., Ambudkar, S.V., Gottesman, M.M., A “silent” polymorphism in the MDR1 gene changes substrate specificity. Science 315 (2007), 525–528.
100. Kitaoka, Y., Takahashi, Y., Machida, M., Takeda, K., Takemasa, T., Hatta, H., Effect of AMPK activation on monocarboxylate transporter (MCT)1 and MCT4 in denervated muscle. The Journal of Physiological Sciences 64 (2014), 59–64.
101. Kitzmiller, J.P., Mikulik, E.B., Dauki, A.M., Murkherjee, C., Luzum, J.A., Pharmacogenomics of statins: Understanding susceptibility to adverse effects. Pharmacogenomics and Personalized Medicine 9 (2016), 97–106.
102. Knauer, M.J., Urquhart, B.L., Meyer zu Schwabedissen, H.E., Schwarz, U.I., Lemke, C.J., Leake, B.F., et al. Human skeletal muscle drug transporters determine local exposure and toxicity of statins. Circulation Research 106 (2010), 297–306.
103. Kobayashi, M., Role of monocarboxylate transporter in statin-induced cytotoxicity. Yakugaku Zasshi 135 (2015), 1227–1233.
104. Kobayashi, M., Fujita, I., Itagaki, S., Hirano, T., Iseki, K., Transport mechanism for L-lactic acid in human myocytes using human prototypic embryonal rhabdomyosarcoma cell line (RD cells). Biological & Pharmaceutical Bulletin 28 (2005), 1197–1201.
105. Kobayashi, M., Hidaka, K., Chisaki, I., Takahashi, N., Ogura, J., Itagaki, S., et al. Effects of acidification and alkalinization agents on statins-induced muscle toxicity. Yakugaku Zasshi 132 (2012), 609–615.
106. Kobayashi, M., Otsuka, Y., Itagaki, S., Hirano, T., Iseki, K., Inhibitory effects of statins on human monocarboxylate transporter 4. International Journal of Pharmaceutics 317 (2006), 19–25.
107. Koch, A.J., Pereira, R., Machado, M., The creatine kinase response to resistance exercise. Journal of Musculoskeletal & Neuronal Interactions 14 (2014), 68–77.
108. Kou, R., Sartoretto, J., Michel, T., Regulation of Rac1 by simvastatin in endothelial cells: differential roles of AMP-activated protein kinase and calmodulin-dependent kinase kinase-beta. The Journal of Biological Chemistry 284 (2009), 14734–14743.
109. Kroetz, D.L., Pauli-Magnus, C., Hodges, L.M., Huang, C.C., Kawamoto, M., Johns, S.J., et al. Sequence diversity and haplotype structure in the human ABCB1 (MDR1, multidrug resistance transporter) gene. Pharmacogenetics 13 (2003), 481–494.
110. Kunze, A., Huwyler, J., Camenisch, G., Poller, B., Prediction of organic anion-transporting polypeptide 1B1- and 1B3-mediated hepatic uptake of statins based on transporter protein expression and activity data. Drug Metabolism and Disposition 42 (2014), 1514–1521.
111. Kwak, H.B., Thalacker-Mercer, A., Anderson, E.J., Lin, C.T., Kane, D.A., Lee, N.S., et al. Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes. Free Radical Biology & Medicine 52 (2012), 198–207.
112. Lee, H.K., Hu, M., Lui, S.S., Ho, C.S., Wong, C.K., Tomlinson, B., Effects of polymorphisms in ABCG2, SLCO1B1, SLC10A1 and CYP2C9/19 on plasma concentrations of rosuvastatin and lipid response in Chinese patients. Pharmacogenomics 14 (2013), 1283–1294.
113. Leusink, M., Onland-Moret, N.C., de Bakker, P.I., de Boer, A., Maitland-van der Zee, A.H., Seventeen years of statin pharmacogenetics: A systematic review. Pharmacogenomics 17 (2016), 163–180.
114. 2 +-release system. The Journal of Pharmacology and Experimental Therapeutics 321 (2007), 626–634.
115. Linde, R., Peng, L., Desai, M., Feldman, D., The role of vitamin D and SLCO1B1 ∗ 5 gene polymorphism in statin-associated myalgias. Dermato-Endocrinology 2 (2010), 77–84.
116. Link, E., Parish, S., Armitage, J., Bowman, L., Heath, S., Matsuda, F., et al. SLCO1B1 variants and statin-induced myopathy—A genomewide study. The New England Journal of Medicine 359 (2008), 789–799.
117. Loenneke, J.P., Loprinzi, P.D., Statin use may reduce lower extremity peak force via reduced engagement in muscle-strengthening activities. Clinical Physiology and Functional Imaging, 2016, Jun 10, 10.1111/cpf.12375 (Epub ahead of print).
118. Lou, X.Y., Zhang, W., Wang, G., Hu, D.L., Guo, D., Tan, Z.R., et al. The effect of Na +/taurocholate cotransporting polypeptide (NTCP) c.800C > T polymorphism on rosuvastatin pharmacokinetics in Chinese healthy males. Pharmazie 69 (2014), 775–779.
119. Madungwe, N.B., Zilberstein, N.F., Feng, Y., Bopassa, J.C., Critical role of mitochondrial ROS is dependent on their site of production on the electron transport chain in ischemic heart. American Journal of Cardiovascular Disease 6 (2016), 93–108.
120. Maeda, K., Ieiri, I., Yasuda, K., Fujino, A., Fujiwara, H., Otsubo, K., et al. Effects of organic anion transporting polypeptide 1B1 haplotype on pharmacokinetics of pravastatin, valsartan, and temocapril. Clinical Pharmacology and Therapeutics 79 (2006), 427–439.
121. Malavaki, C.J., Sakkas, G.K., Mitrou, G.I., Kalyva, A., Stefanidis, I., Myburgh, K.H., Karatzaferi, C., Skeletal muscle atrophy: Disease-induced mechanisms may mask disuse atrophy. Journal of Muscle Research and Cell Motility 36 (2015), 405–421.
122. Mallinson, J.E., Constantin-Teodosiu, D., Glaves, P.D., Martin, E.A., Davies, W.J., Westwood, F.R., et al. Pharmacological activation of the pyruvate dehydrogenase complex reduces statin-mediated upregulation of FOXO gene targets and protects against statin myopathy in rodents. The Journal of Physiology 590 (2012), 6389–6402.
123. Mallinson, J.E., Constantin-Teodosiu, D., Sidaway, J., Westwood, F.R., Greenhaff, P.L., Blunted Akt/FOXO signalling and activation of genes controlling atrophy and fuel use in statin myopathy. The Journal of Physiology 587 (2009), 219–230.
124. Mancini, G.B., Baker, S., Bergeron, J., Fitchett, D., Fröhlich, J., Genest, J., et al. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian consensus working group update. The Canadian Journal of Cardiology 32:7 Suppl (2016), S35–S65.
125. Massidda, M., Eynon, N., Bachis, V., Corrias, L., Culigioni, C., Piras, F., et al. Influence of the MCT1 rs1049434 on indirect muscle disorders/injuries in elite football players. Sports Medicine - Open, 1, 2015, 33.
126. Masters, B.A., Palmoski, M.J., Flint, O.P., Gregg, R.E., Wang-Iverson, D., Durham, S.K., In vitro myotoxicity of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, pravastatin, lovastatin, and simvastatin, using neonatal rat skeletal myocytes. Toxicology and Applied Pharmacology 131 (1995), 163–174.
127. Merezhinskaya, N., Fishbein, W.N., Davis, J.I., Foellmer, J.W., Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport. Muscle & Nerve 23 (2000), 90–97.
128. Mergenhagen, K., Ott, M., Heckman, K., Rubin, L.M., Kellick, K., Low vitamin D as a risk factor for the development of myalgia in patients taking high-dose simvastatin: A retrospective review. Clinical Therapeutics 36 (2014), 770–777.
129. Meyer zu Schwabedissen, H.E., Kroemer, H.K., In vitro and in vivo evidence for the importance of breast cancer resistance protein transporters (BCRP/MXR/ABCP/ABCG2). Handbook of Experimental Pharmacology 201 (2011), 325–371.
130. Michalska-Kasiczak, M., Sahebkar, A., Mikhailidis, D.P., Rysz, J., Muntner, P., Toth, P.P., et al. Analysis of vitamin D levels in patients with and without statin-associated myalgia — A systematic review and meta-analysis of 7 studies with 2420 patients. International Journal of Cardiology 178 (2015), 111–116.
131. Millan, M.J., The induction of pain: an integrative review. Progress in Neurobiology 57 (1999), 1–164.
132. Mirošević Skvrce, N., Macolić Šarinić, V., Šimić, I., Ganoci, L., Muačević Katanec, D., Božina, N., ABCG2 gene polymorphisms as risk factors for atorvastatin adverse reactions: A case-control study. Pharmacogenomics 16 (2015), 803–815.
133. Mohaupt, M.G., Karas, R.H., Babiychuk, E.B., Sanchez-Freire, V., Monastyrskaya, K., Iyer, L., et al. Association between statin-associated myopathy and skeletal muscle damage. CMAJ 181 (2009), E11–E18.
134. Morales-Alamo, D., Calbet, J.A., AMPK signaling in skeletal muscle during exercise: Role of reactive oxygen and nitrogen species. Free Radical Biology & Medicine 98 (2016), 68–77.
135. Mori, M., Yamagata, T., Goto, T., Saito, S., Momoi, M.Y., Dichloroacetate treatment for mitochondrial cytopathy: Long-term effects in MELAS. Brain and Development 26 (2004), 453–458.
136. Morikawa, S., Murakami, T., Yamazaki, H., Izumi, A., Saito, Y., Hamakubo, T., Kodama, T., Analysis of the global RNA expression profiles of skeletal muscle cells treated with statins. Journal of Atherosclerosis and Thrombosis 12 (2005), 121–131.
137. Morioka, T.Y., Lee, A.J., Bertisch, S., Buettner, C., Vitamin D status modifies the association between statin use and musculoskeletal pain: A population based study. Atherosclerosis 238 (2015), 77–82.
138. Mullen, P.J., Lüscher, B., Scharnagl, H., Krähenbühl, S., Brecht, K., Effect of simvastatin on cholesterol metabolism in C2C12 myotubes and HepG2 cells, and consequences for statin-induced myopathy. Biochemical Pharmacology 79 (2010), 1200–1209.
139. Mullen, P.J., Zahno, A., Lindinger, P., Maseneni, S., Felser, A., Krähenbühl, S., Brecht, K., Susceptibility to simvastatin-induced toxicity is partly determined by mitochondrial respiration and phosphorylation state of Akt. Biochimica et Biophysica Acta 1813 (2011), 2079–2087.
140. Muntean, D.M., Thompson, P.D., Catapano, A.L., Stasiolek, M., Fabis, J., Muntner, P., et al. Statin-associated myopathy and the quest for biomarkers: can we effectively predict statin-associated muscle symptoms?. Drug Discovery Today 22 (2017), 85–96.
141. Muraki, A., Miyashita, K., Mitsuishi, M., Tamaki, M., Tanaka, K., Itoh, H., Coenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance. Journal of Applied Physiology (1985) 113 (2012), 479–486.
142. Nagasawa, K., Nagai, K., Ishimoto, A., Fujimoto, S., Transport mechanism for lovastatin acid in bovine kidney NBL-1 cells: kinetic evidences imply involvement of monocarboxylate transporter 4. International Journal of Pharmaceutics 262 (2003), 63–73.
143. Nagasawa, K., Nagai, K., Sumitani, Y., Moriya, Y., Muraki, Y., Takara, K., et al. Monocarboxylate transporter mediates uptake of lovastatin acid in rat cultured mesangial cells. Journal of Pharmaceutical Sciences 91 (2002), 2605–2613.
144. Neřoldová, M., Stránecký, V., Hodaňová, K., Hartmannová, H., Piherová, L., Přistoupilová, A., et al. Rare variants in known and novel candidate genes predisposing to statin-associated myopathy. Pharmacogenomics 17 (2016), 1405–1414.
145. Niemi, M., Pasanen, M.K., Neuvonen, P.J., SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatin. Clinical Pharmacology and Therapeutics 80 (2006), 356–366.
146. Nies, A.T., Niemi, M., Burk, O., Winter, S., Zanger, U.M., Stieger, B., et al. Genetics is a major determinant of expression of the human hepatic uptake transporter OATP1B1, but not of OATP1B3 and OATP2B1. Genome Medicine, 5, 2013, 1.
147. Oh, E.S., Kim, C.O., Cho, S.K., Park, M.S., Chung, J.Y., Impact of ABCC2, ABCG2 and SLCO1B1 polymorphisms on the pharmacokinetics of pitavastatin in humans. Drug Metabolism and Pharmacokinetics 28 (2013), 196–202.
148. Osaki, Y., Nakagawa, Y., Miyahara, S., Iwasaki, H., Ishii, A., Matsuzaka, T., et al. Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy. Biochemical and Biophysical Research Communications 466 (2015), 536–540.
149. Ovesjö, M.L., Skilving, I., Bergman, P., Rane, A., Ekström, L., Björkhem-Bergman, L., Low vitamin D levels and genetic polymorphism in the vitamin D receptor are associated with increased risk of statin-induced myopathy. Basic & Clinical Pharmacology & Toxicology 118 (2016), 214–218.
150. Päivä, H., Thelen, K.M., Van Coster, R., Smet, J., De Paepe, B., Mattila, K.M., et al. High-dose statins and skeletal muscle metabolism in humans: A randomized, controlled trial. Clinical Pharmacology and Therapeutics 78 (2005), 60–68.
151. Palamaner Subash Shantha, G., Ramos, J., Thomas-Hemak, L., Pancholy, S.B., Association of vitamin D and incident statin induced myalgia—A retrospective cohort study. PLoS One, 9, 2014, e88877.
152. Pasanen, M.K., Neuvonen, M., Neuvonen, P.J., Niemi, M., SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. Pharmacogenetics and Genomics 16 (2006), 873–879.
153. Pedro-Botet, J., Millán Núñez-Cortés, J., Chillarón, J.J., Flores-Le Roux, J.A., Rius, J., Severity of statin-induced adverse effects on muscle and associated conditions: data from the DAMA study. Expert Opinion on Drug Safety, 2016, Oct 24, 1–5 (Epub ahead of print).
154. Pereda, C.A., Nishishinya, M.B., Is there really a relationship between serum vitamin D (25OHD) levels and the musculoskeletal pain associated with statin intake? A systematic review. Reumatología Clínica 12 (2016), 331–335.
155. Phillips, P.S., Haas, R.H., Bannykh, S., Hathaway, S., Gray, N.L., Kimura, B.J., et al. Statin-associated myopathy with normal creatine kinase levels. Annals of Internal Medicine 137 (2002), 581–585.
156. Pierno, S., Camerino, G.M., Cippone, V., Rolland, J.F., Desaphy, J.F., De Luca, A., et al. Statins and fenofibrate affect skeletal muscle chloride conductance in rats by differently impairing ClC-1 channel regulation and expression. British Journal of Pharmacology 156 (2009), 1206–1215.
157. Pollak, K.A., Swenson, J.D., Vanhaitsma, T.A., Hughen, R.W., Jo, D., White, A.T., et al. Exogenously applied muscle metabolites synergistically evoke sensations of muscle fatigue and pain in human subjects. Experimental Physiology 99 (2014), 368–380.
158. Ramsey, L.B., Johnson, S.G., Caudle, K.E., Haidar, C.E., Voora, D., Wilke, R.A., et al. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clinical Pharmacology and Therapeutics 96 (2014), 423–428.
159. Robinson, J.G., Farnier, M., Krempf, M., Bergeron, J., Luc, G., Averna, M., et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. The New England Journal of Medicine 372 (2015), 1489–1499.
160. Rodrigues, A.C., Efflux and uptake transporters as determinants of statin response. Expert Opinion on Drug Metabolism & Toxicology 6 (2010), 621–632.
161. Rodrigue-Way, A., Caron, V., Bilodeau, S., Keil, S., Hassan, M., Lévy, E., et al. Scavenger receptor CD36 mediates inhibition of cholesterol synthesis via activation of the PPARγ/PGC-1α pathway and Insig1/2 expression in hepatocytes. The FASEB Journal 28 (2014), 1910–1923.
162. Rosendal, L., Larsson, B., Kristiansen, J., Peolsson, M., Søgaard, K., Kjaer, M., et al. Increase in muscle nociceptive substances and anaerobic metabolism in patients with trapezius myalgia: microdialysis in rest and during exercise. Pain 112 (2004), 324–334.
163. Rotto, D.M., Kaufman, M.P., Effect of metabolic products of muscular contraction on discharge of group III and IV afferents. Journal of Applied Physiology (1985) 64 (1988), 2306–2313.
164. Sabatine, M.S., Giugliano, R.P., Wiviott, S.D., Raal, F.J., Blom, D.J., Robinson, J., et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. The New England Journal of Medicine 372 (2015), 1500–1509.
165. Sahebkar, A., Reiner, Ž., Simental-Mendía, L.E., Ferretti, G., Corte, C.D., Nobili, V., Impact of statin therapy on plasma vitamin D levels: A systematic review and meta-analysis. Current Pharmaceutical Design, 2016, Oct 6 (Epub ahead of print).
166. Sakamoto, K., Honda, T., Yokoya, S., Waguri, S., Kimura, J., Rab-small GTPases are involved in fluvastatin and pravastatin-induced vacuolation in rat skeletal myofibers. The FASEB Journal 21 (2007), 4087–4094.
167. Salles, J., Chanet, A., Giraudet, C., Patrac, V., Pierre, P., Jourdan, M., et al. 1,25(OH)2-vitamin D3 enhances the stimulating effect of leucine and insulin on protein synthesis rate through Akt/PKB and mTOR mediated pathways in murine C2C12 skeletal myotubes. Molecular Nutrition & Food Research 57 (2013), 2137–2146.
168. Sandri, M., Lin, J., Handschin, C., Yang, W., Arany, Z.P., Lecker, S.H., et al. PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Proceedings of the National Academy of Sciences of the United States of America 103 (2006), 16260–16265.
169. Santos, P.C., Gagliardi, A.C., Miname, M.H., Chacra, A.P., Santos, R.D., Krieger, J.E., Pereira, A.C., SLCO1B1 haplotypes are not associated with atorvastatin-induced myalgia in Brazilian patients with familial hypercholesterolemia. European Journal of Clinical Pharmacology 68 (2012), 273–279.
170. Saxon, D.R., Eckel, R.H., Statin intolerance: A literature review and management strategies. Progress in Cardiovascular Diseases 59 (2016), 153–164.
171. Schachter, M., Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundamental & Clinical Pharmacology 19 (2005), 117–125.
172. Schick, B.A., Laaksonen, R., Frohlich, J.J., Päivä, H., Lehtimäki, T., Humphries, K.H., Côté, H.C., Decreased skeletal muscle mitochondrial DNA in patients treated with high-dose simvastatin. Clinical Pharmacology and Therapeutics 81 (2007), 650–653.
173. Schirris, T.J., Renkema, G.H., Ritschel, T., Voermans, N.C., Bilos, A., van Engelen, B.G., et al. Statin-induced myopathy is associated with mitochondrial complex III inhibition. Cell Metabolism 22 (2015), 399–407.
174. Shirasaka, Y., Suzuki, K., Shichiri, M., Nakanishi, T., Tamai, I., Intestinal absorption of HMG-CoA reductase inhibitor pitavastatin mediated by organic anion transporting polypeptide and P-glycoprotein/multidrug resistance 1. Drug Metabolism and Pharmacokinetics 26 (2011), 171–179.
175. Shitara, Y., Sugiyama, Y., Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors: Drug-drug interactions and interindividual differences in transporter and metabolic enzyme functions. Pharmacology & Therapeutics 112 (2006), 71–105.
176. Silva, M.A., Swanson, A.C., Gandhi, P.J., Tataronis, G.R., Statin-related adverse events: A meta-analysis. Clinical Therapeutics 28 (2006), 26–35.
177. Sirvent, P., Fabre, O., Bordenave, S., Hillaire-Buys, D., Raynaud De Mauverger, E., Lacampagne, A., Mercier, J., Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins. Toxicology and Applied Pharmacology 259 (2012), 263–268.
178. 2 + signaling alteration in skeletal muscle. Biochemical and Biophysical Research Communications 329 (2005), 1067–1075.
179. Skarlovnik, A., Janić, M., Lunder, M., Turk, M., Šabovič, M., Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study. Medical Science Monitor 20 (2014), 2183–2188.
180. Skilving, I., Acimovic, J., Rane, A., Ovesjö, M.L., Björkhem-Bergman, L., Statin-induced myopathy and ubiquinone levels in serum — results from a prospective, observational study. Basic & Clinical Pharmacology & Toxicology 117 (2015), 133–136.
181. Skilving, I., Eriksson, M., Rane, A., Ovesjö, M.L., Statin-induced myopathy in a usual care setting-a prospective observational study of gender differences. European Journal of Clinical Pharmacology 72 (2016), 1171–1176.
182. Slade, J.M., Delano, M.C., Meyer, R.A., Elevated skeletal muscle phosphodiesters in adults using statin medications. Muscle & Nerve 34 (2006), 782–784.
183. Smith, J.A., Kohn, T.A., Chetty, A.K., Ojuka, E.O., CaMK activation during exercise is required for histone hyperacetylation and MEF2A binding at the MEF2 site on the Glut4 gene. American Journal of Physiology. Endocrinology and Metabolism 295 (2008), E698–E704.
184. St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J.M., Rhee, J., Jäger, S., et al. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127 (2006), 397–408.
185. Stránecký, V., Neřoldová, M., Hodaňová, K., Hartmannová, H., Piherová, L., Zemánková, P., et al. Large copy-number variations in patients with statin-associated myopathy affecting statin myopathy-related loci. Physiological Research 65 (2016), 1005–1011.
186. Stroes, E.S., Thompson, P.D., Corsini, A., Vladutiu, G.D., Raal, F.J., Ray, K.K., et al. Statin-associated muscle symptoms: impact on statin therapy-european atherosclerosis society consensus panel statement on assessment, aetiology and management. European Heart Journal 36 (2015), 1012–1022.
187. Su, J., Xu, H., Yang, J., Yu, Q., Yang, S., Zhang, J., et al. ABCB1 C3435T polymorphism and the lipid-lowering response in hypercholesterolemic patients on statins: a meta-analysis. Lipids in Health and Disease, 14, 2015, 122.
188. Summermatter, S., Santos, G., Pérez-Schindler, J., Handschin, C., Skeletal muscle PGC-1α controls whole-body lactate homeostasis through estrogen-related receptor α-dependent activation of LDH B and repression of LDH A. Proceedings of the National Academy of Sciences of the United States of America 110 (2013), 8738–8743.
189. Sun, W., Lee, T.S., Zhu, M., Gu, C., Wang, Y., Zhu, Y., Shyy, J.Y., Statins activate AMP-activated protein kinase in vitro and in vivo. Circulation 114 (2006), 2655–2662.
190. Suneja, M., Fox, D.K., Fink, B.D., Herlein, J.A., Adams, C.M., Sivitz, W.I., Evidence for metabolic aberrations in asymptomatic persons with type 2 diabetes after initiation of simvastatin therapy. Translational Research 166 (2015), 176–187.
191. Svensson, K., Albert, V., Cardel, B., Salatino, S., Handschin, C., Skeletal muscle PGC-1α modulates systemic ketone body homeostasis and ameliorates diabetic hyperketonemia in mice. The FASEB Journal 30 (2016), 1976–1986.
192. Tang, C.Y., Chen, T.Y., Physiology and pathophysiology of CLC-1: Mechanisms of a chloride channel disease, myotonia. Journal of Biomedicine & Biotechnology, 2011, 2011, 685328.
193. Taylor, B.A., Lorson, L., White, C.M., Thompson, P.D., A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy. Atherosclerosis 238 (2015), 329–335.
194. Teng, M., Lin, L., Zhao, Y.J., Khoo, A.L., Davis, B.R., Yong, Q.W., et al. Statins for primary prevention of cardiovascular disease in elderly patients: Systematic review and meta-analysis. Drugs & Aging 32 (2015), 649–661.
195. Thai, M., Reeve, E., Hilmer, S.N., Qi, K., Pearson, S.A., Gnjidic, D., Prevalence of statin-drug interactions in older people: A systematic review. European Journal of Clinical Pharmacology 72 (2016), 513–521.
196. Thiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M.M., Pastan, I., Willingham, M.C., Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: Evidence for localization in brain capillaries and cross reactivity of one antibody with a muscle protein. The Journal of Histochemistry and Cytochemistry 37 (1989), 159–164.
197. Thomas, C., Perrey, S., Lambert, K., Hugon, G., Mornet, D., Mercier, J., Monocarboxylate transporters, blood lactate removal after supramaximal exercise, and fatigue indexes in humans. Journal of Applied Physiology (1985) 98 (2005), 804–889.
198. Tornio, A., Vakkilainen, J., Neuvonen, M., Backman, J.T., Neuvonen, P., Niemi, M., SLCO1B1 polymorphism markedly affects the pharmacokinetics of lovastatin acid. Pharmacogenetics and Genomics 25 (2015), 382–387.
199. Urso, M.L., Clarkson, P.M., Hittel, D., Hoffman, E.P., Thompson, P.D., Changes in ubiquitin proteasome pathway gene expression in skeletal muscle with exercise and statins. Arteriosclerosis, Thrombosis, and Vascular Biology 25 (2005), 2560–2566.
200. Vandenboom, R., The myofibrillar complex and fatigue: A review. Canadian Journal of Applied Physiology 29 (2004), 330–356.
201. Varikmaa, M., Bagur, R., Kaambre, T., Grichine, A., Timohhina, N., Tepp, K., et al. Role of mitochondria-cytoskeleton interactions in respiration regulation and mitochondrial organization in striated muscles. Biochimica et Biophysica Acta 1837 (2014), 232–245.
202. Vaughan, R.A., Garcia-Smith, R., Bisoffi, M., Conn, C.A., Trujillo, K.A., Ubiquinol rescues simvastatin-suppression of mitochondrial content, function and metabolism: Implications for statin-induced rhabdomyolysis. European Journal of Pharmacology 711 (2013), 1–9.
203. Voora, D., Shah, S.H., Spasojevic, I., Ali, S., Reed, C.R., Salisbury, B.A., Ginsburg, G.S., The SLCO1B1 ∗ 5 genetic variant is associated with statin-induced side effects. Journal of the American College of Cardiology 54 (2009), 1609–1616.
204. Wagatsuma, A., Shiozuka, M., Takayama, Y., Hoshino, T., Mabuchi, K., Matsuda, R., Effects of ageing on expression of the muscle-specific E3 ubiquitin ligases and Akt-dependent regulation of Foxo transcription factors in skeletal muscle. Molecular and Cellular Biochemistry 412 (2016), 59–72.
205. Wallach-Kildemoes, H., Stovring, H., Holme Hansen, E., Howse, K., Pétursson, H., Statin prescribing according to gender, age and indication: What about the benefit-risk balance?. Journal of Evaluation in Clinical Practice 22 (2016), 235–246.
206. Wan, Z., Wang, G., Li, T., Xu, B., Pei, Q., Peng, Y., et al. Marked alteration of rosuvastatin pharmacokinetics in healthy Chinese with ABCG2 34G > A and 421C > A homozygote or compound heterozygote. The Journal of Pharmacology and Experimental Therapeutics 354 (2015), 310–315.
207. Wilke, R.A., Moore, J.H., Burmester, J.K., Relative impact of CYP3A genotype and concomitant medication on the severity of atorvastatin-induced muscle damage. Pharmacogenetics and Genomics 15 (2005), 415–421.
208. Zhang, H., Plutzky, J., Skentzos, S., Morrison, F., Mar, P., Shubina, M., Turchin, A., Discontinuation of statins in routine care settings: A cohort study. Annals of Internal Medicine 158 (2013), 526–534.
209. Zhang, Y., Uguccioni, G., Ljubicic, V., Irrcher, I., Iqbal, S., Singh, K., et al. Multiple signaling pathways regulate contractile activity-mediated PGC-1α gene expression and activity in skeletal muscle cells. Physiological Reports, 2, 2014 (pii: e12008).
210. Zheng, B., Ohkawa, S., Li, H., Roberts-Wilson, T.K., Price, S.R., FOXO3a mediates signaling crosstalk that coordinates ubiquitin and atrogin-1/MAFbx expression during glucocorticoid-induced skeletal muscle atrophy. The FASEB Journal 24 (2010), 2660–2669.
211. Zhou, Q., Chen, Q.X., Ruan, Z.R., Yuan, H., Xu, H.M., Zeng, S., CYP2C9 ∗ 3(1075A > C), ABCB1 and SLCO1B1 genetic polymorphisms and gender are determinants of inter-subject variability in pitavastatin pharmacokinetics. Pharmazie 68 (2013), 187–194.
212. Zhou, Q., Ruan, Z.R., Jiang, B., Yuan, H., Zeng, S., Simvastatin pharmacokinetics in healthy Chinese subjects and its relations with CYP2C9, CYP3A5, ABCB1, ABCG2 and SLCO1B1 polymorphisms. Pharmazie 68 (2013), 124–128.
213. Zhou, Q., Ruan, Z.R., Yuan, H., Xu, D.H., Zeng, S., ABCB1 gene polymorphisms, ABCB1 haplotypes and ABCG2 c.421c > A are determinants of inter-subject variability in rosuvastatin pharmacokinetics. Pharmazie 68 (2013), 129–134.