Cytostatic Effect of Repeated Exposure to Simvastatin: A Mechanism for Chronic Myotoxicity Revealed by the Use of Mesodermal Progenitors Derived from Human Pluripotent Stem Cells

Stem Cells

Volumn 33, Issue 10, 2015, Pages 2936-2948

  Peric, Delphine ^a   Barragan, Isabel ^b   Giraud Triboult, Karine ^a   Egesipe, Anne Laure ^a   Meyniel Schicklin, Laurène ^c   Cousin, Christelle ^d   Lotteau, Vincent ^c   Petit, Vincent ^d   Touhami, Jawida ^e   Battini, Jean Luc ^e   Sitbon, Marc ^e   Pinset, Christian ^a   Ingelman Sundberg, Magnus ^b   Laustriat, Delphine ^a   Peschanski, Marc ^a  

^a I Stem   (France)

^b KAROLINSKA INSTITUTE   (Sweden)

^c CENTRE INTERNATIONAL DE RECHERCHE EN INFECTIOLOGIE   (France)

^d METAFORA Biosystems   (France)

^e INSTITUT DE GÉNÉTIQUE MOLÉCULAIRE DE MONTPELLIER   (France)

Author keywords

Chronic toxicity; Cytostatic agent; Mesoderm; Pluripotent stem cells; Simvastatin

Indexed keywords

ATORVASTATIN; CERIVASTATIN; CYTOSTATIC AGENT; FLUINDOSTATIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; MEVALONIC ACID; MEVINOLIN; PRAVASTATIN; SIMVASTATIN; TRANSCRIPTOME;

ACUTE TOXICITY; ADAPTATION; ANIMAL CELL; ARTICLE; CELL DEATH; CELL DIFFERENTIATION; CELL PROLIFERATION; CHRONIC TOXICITY; CONTROLLED STUDY; CYTOSTASIS; DOSE RESPONSE; EMBRYO; FLOW CYTOMETRY; GENE EXPRESSION; GENOME; HYPERCHOLESTEROLEMIA; IN VITRO STUDY; LONG TERM EXPOSURE; MESODERM; MESODERMAL CELL; MOUSE; MYOBLAST; MYOPATHY; MYOTOXICITY; NONHUMAN; PLURIPOTENT STEM CELL; REPEATED DRUG DOSE; STEM CELL CULTURE; CELL LINE; COMPLICATION; CYTOLOGY; DRUG EFFECTS; GENE EXPRESSION REGULATION; HUMAN; PATHOLOGY; SKELETAL MUSCLE;

CELL DIFFERENTIATION; CELL LINE; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, DRUG; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HUMANS; HYPERCHOLESTEROLEMIA; MESODERM; MUSCLE, SKELETAL; PLURIPOTENT STEM CELLS; SIMVASTATIN; TRANSCRIPTOME;

EID: 84942367879     PISSN: 10665099     EISSN: 15494918     Source Type: Journal    
DOI: 10.1002/stem.2107     Document Type: Article

References (58)

1. Mihos CG, Pineda AM, Santana O,. Cardiovascular effects of statins, beyond lipid-lowering properties. Pharmacol Res 2014; 88: 12-19.
2. Corsini A, Maggi FM, Catapano AL,. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol Res 1995; 31: 9-27.
3. Thompson PD, Clarkson P, Karas RH,. Statin-associated myopathy. JAMA 2003; 289: 1681-1690.
4. Furberg CD, Pitt B,. Withdrawal of cerivastatin from the world market. Curr Control Trials Cardiovasc Med 2001; 2: 205-207.
5. Vaklavas C, Chatzizisis YS, Ziakas A, et al., Molecular basis of statin-associated myopathy. Atherosclerosis 2009; 202: 18-28.
6. Kwak HB, Thalacker-Mercer A, Anderson EJ, et al., Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes. Free Radic Biol Med 2012; 52: 198-207.
7. Sacher J, Weigl L, Werner M, et al., Delineation of myotoxicity induced by 3-hydroxy-3-methylglutaryl CoA reductase inhibitors in human skeletal muscle cells. J Pharmacol Exp Ther 2005; 314: 1032-1041.
8. Nishimoto T, Tozawa R, Amano Y, et al., Comparing myotoxic effects of squalene synthase inhibitor, T-91485, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in human myocytes. Biochem Pharmacol 2003; 66: 2133-2139.
9. Hanai J, Cao P, Tanksale P, et al., The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. J Clin Invest 2007; 117: 3940-3951.
10. Trapani L, Segatto M, La Rosa P, et al., 3-hydroxy 3-methylglutaryl coenzyme A reductase inhibition impairs muscle regeneration. J Cell Biochem 2012; 113: 2057-2063.
11. Masters BA, Palmoski MJ, Flint OP, et al., In vitro myotoxicity of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, pravastatin, lovastatin, and simvastatin, using neonatal rat skeletal myocytes. Toxicol Appl Pharmacol 1995; 131: 163-174.
12. Sakamoto K, Honda T, Yokoya S, et al., Rab-small GTPases are involved in fluvastatin and pravastatin-induced vacuolation in rat skeletal myofibers. FASEB J 2007; 21: 4087-4094.
13. Itagaki M, Takaguri A, Kano S, et al., Possible mechanisms underlying statin-induced skeletal muscle toxicity in L6 fibroblasts and in rats. J Pharmacol Sci 2009; 109: 94-101.
14. Johnson TE, Zhang X, Bleicher KB, et al., Statins induce apoptosis in rat and human myotube cultures by inhibiting protein geranylgeranylation but not ubiquinone. Toxicol Appl Pharmacol 2004; 200: 237-250.
15. Mullen PJ, Luscher B, Scharnagl H, et al., Effect of simvastatin on cholesterol metabolism in C2C12 myotubes and HepG2 cells, and consequences for statin-induced myopathy. Biochem Pharmacol 2010; 79: 1200-1209.
16. Sakamoto K, Mikami H, Kimura J,. Involvement of organic anion transporting polypeptides in the toxicity of hydrophilic pravastatin and lipophilic fluvastatin in rat skeletal myofibres. Br J Pharmacol 2008; 154: 1482-1490.
17. Barberi T, Bradbury M, Dincer Z, et al., Derivation of engraftable skeletal myoblasts from human embryonic stem cells. Nat Med 2007; 13: 642-648.
18. Giraud-Triboult K, Rochon-Beaucourt C, Nissan X, et al., Combined mRNA and microRNA profiling reveals that miR-148a and miR-20b control human mesenchymal stem cell phenotype via EPAS1. Physiol Genomics 2011; 43: 77-86.
19. Li J, Cousin C, Tinkler H, et al., Profiling of nutrient transporter expression in human stem cell-derived cardiomyocytes exposed to tyrosine kinase inhibitor anticancer drugs using RBD ligands. J Biomol Screen 2014; 19: 1185-1192.
20. van Vliet AK, Negre-Aminou P, van Thiel GC, et al., Action of lovastatin, simvastatin, and pravastatin on sterol synthesis and their antiproliferative effect in cultured myoblasts from human striated muscle. Biochem Pharmacol 1996; 52: 1387-1392.
21. Lagrue E, Abe H, Lavanya M, et al., Regional characterization of energy metabolism in the brain of normal and MPTP-intoxicated mice using new markers of glucose and phosphate transport. J Biomed Sci 2010; 17: 91.
22. Laval J, Touhami J, Herzenberg LA, et al., Metabolic adaptation of neutrophils in cystic fibrosis airways involves distinct shifts in nutrient transporter expression. J Immunol 2013; 190: 6043-6050.
23. Manel N, Kim FJ, Kinet S, et al., The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV. Cell 2003; 115: 449-459.
24. Montel-Hagen A, Blanc L, Boyer-Clavel M, et al., The Glut1 and Glut4 glucose transporters are differentially expressed during perinatal and postnatal erythropoiesis. Blood 2008; 112: 4729-4738.
25. Oburoglu L, Tardito S, Fritz V, et al., Glucose and glutamine metabolism regulate human hematopoietic stem cell lineage specification. Cell Stem Cell 2014; 15: 169-184.
26. Swainson L, Kinet S, Manel N, et al., Glucose transporter 1 expression identifies a population of cycling CD4+ CD8+ human thymocytes with high CXCR4-induced chemotaxis. Proc Natl Acad Sci USA 2005; 102: 12867-12872.
27. Giovannini D, Touhami J, Charnet P, et al., Inorganic phosphate export by the retrovirus receptor XPR1 in metazoans. Cell Rep 2013; 3: 1866-1873.
28. Gomes MD, Lecker SH, Jagoe RT, et al., Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci USA 2001; 98: 14440-14445.
29. Tanaka S, Sakamoto K, Yamamoto M, et al., Mechanism of statin-induced contractile dysfunction in rat cultured skeletal myofibers. J Pharmacol Sci 2010; 114: 454-463.
30. Vaughan RA, Garcia-Smith R, Bisoffi M, et al., Ubiquinol rescues simvastatin-suppression of mitochondrial content, function and metabolism: Implications for statin-induced rhabdomyolysis. Eur J Pharmacol 2013; 711: 1-9.
31. Bellosta S, Paoletti R, Corsini A,. Safety of statins: Focus on clinical pharmacokinetics and drug interactions. Circulation 2004; 109: III50-57.
32. Tedesco FS, Dellavalle A, Diaz-Manera J, et al., Repairing skeletal muscle: Regenerative potential of skeletal muscle stem cells. J Clin Invest 2010; 120: 11-19.
33. Thompson PD, Zmuda JM, Domalik LJ, et al., Lovastatin increases exercise-induced skeletal muscle injury. Metabolism 1997; 46: 1206-1210.
34. Seachrist JL, Loi CM, Evans MG, et al., Roles of exercise and pharmacokinetics in cerivastatin-induced skeletal muscle toxicity. Toxicol Sci 2005; 88: 551-561.
35. Chrysanthopoulos C, Kounis N,. Rhabdomyolysis due to combined treatment with lovastatin and cholestyramine. BMJ 1992; 304: 1225.
36. Sinzinger H, Schmid P, O'Grady J,. Two different types of exercise-induced muscle pain without myopathy and CK-elevation during HMG-Co-enzyme-A-reductase inhibitor treatment. Atherosclerosis 1999; 143: 459-460.
37. Unnikrishnan D, Satish B,. Exertion-induced rhabdomyolysis in a patient on statin therapy. Nephrol Dial Transplant 2005; 20: 244.
38. Sinzinger H, O'Grady J,. Professional athletes suffering from familial hypercholesterolaemia rarely tolerate statin treatment because of muscular problems. Br J Clin Pharmacol 2004; 57: 525-528.
39. Belo RS, Jamieson JC, Wright JA,. Studies on the effect of mevinolin (lovastatin) and mevastatin (compactin) on the fusion of L6 myoblasts. Mol Cell Biochem 1993; 126: 159-167.
40. Soininen K, Niemi M, Kilkki E, et al., Muscle symptoms associated with statins: A series of twenty patients. Basic Clin Pharmacol Toxicol 2006; 98: 51-54.
41. Tomlinson SS, Mangione KK,. Potential adverse effects of statins on muscle. Phys Ther 2005; 85: 459-465.
42. Chan KC, Wang CJ, Ho HH, et al., Simvastatin inhibits cell cycle progression in glucose-stimulated proliferation of aortic vascular smooth muscle cells by up-regulating cyclin dependent kinase inhibitors and p53. Pharmacol Res 2008; 58: 247-256.
43. Porter KE, Naik J, Turner NA, et al., Simvastatin inhibits human saphenous vein neointima formation via inhibition of smooth muscle cell proliferation and migration. J Vasc Surg 2002; 36: 150-157.
44. Brown MS, Goldstein JL,. The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 1997; 89: 331-340.
45. Horton JD, Shah NA, Warrington JA, et al., Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci USA 2003; 100: 12027-12032.
46. Sato R, Inoue J, Kawabe Y, et al., Sterol-dependent transcriptional regulation of sterol regulatory element-binding protein-2. J Biol Chem 1996; 271: 26461-26464.
47. Mangravite LM, Engelhardt BE, Medina MW, et al., A statin-dependent QTL for GATM expression is associated with statin-induced myopathy. Nature 2013; 502: 377-380.
48. Medina MW, Gao F, Naidoo D, et al., Coordinately regulated alternative splicing of genes involved in cholesterol biosynthesis and uptake. PLoS One 2011; 6: e19420.
49. Stormo C, Kringen MK, Grimholt RM, et al., A novel 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) splice variant with an alternative exon 1 potentially encoding an extended N-terminus. BMC Mol Biol 2012; 13: 29.
50. Yamasaki D, Nakamura T, Okamura N, et al., Effects of acid and lactone forms of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on the induction of MDR1 expression and function in LS180 cells. Eur J Pharm Sci 2009; 37: 126-132.
51. Urso ML, Chen YW, Scrimgeour AG, et al., Alterations in mRNA expression and protein products following spinal cord injury in humans. J Physiol 2007; 579: 877-892.
52. Leger B, Senese R, Al-Khodairy AW, et al., Atrogin-1, MuRF1, and FoXO, as well as phosphorylated GSK-3beta and 4E-BP1 are reduced in skeletal muscle of chronic spinal cord-injured patients. Muscle Nerve 2009; 40: 69-78.
53. Mallinson JE, Constantin-Teodosiu D, Sidaway J, et al., Blunted Akt/FOXO signalling and activation of genes controlling atrophy and fuel use in statin myopathy. J Physiol 2009; 587: 219-230.
54. Beck L, Leroy C, Beck-Cormier S, et al., The phosphate transporter PiT1 (Slc20a1) revealed as a new essential gene for mouse liver development. PLoS One 2010; 5: e9148.
55. Prieto P, Baird AW, Blaauboer BJ, et al., The assessment of repeated dose toxicity in vitro: A proposed approach. The report and recommendations of ECVAM workshop 56. Altern Lab Anim 2006; 34: 315-341.
56. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al., Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145-1147.
57. Takahashi K, Tanabe K, Ohnuki M, et al., Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131: 861-872.
58. Wobus AM, Loser P,. Present state and future perspectives of using pluripotent stem cells in toxicology research. Arch Toxicol 2011; 85: 79-117.