Opposite effects of statins on mitochondria of cardiac and skeletal muscles: a ‘mitohormesis’ mechanism involving reactive oxygen species and PGC-1
Open accessAbstract
AIMS: Statins protect against cardiovascular-related mortality but induce skeletal muscle toxicity. To investigate mechanisms of statins, we tested the hypothesis that statins optimized cardiac mitochondrial function but impaired vulnerable skeletal muscle by inducing different level of reactive oxygen species (ROS). METHODS AND RESULTS: In atrium of patients treated with statins, ROS production was decreased and oxidative capacities were enhanced together with an extensive augmentation of mRNAs expression of peroxisome proliferator-activated receptor gamma co-activator (PGC-1) family. However, in deltoid biopsies from patients with statin-induced muscular myopathy, oxidative capacities were decreased together with ROS increase and a collapse of PGC-1 mRNA expression. Several animal and cell culture experiments were conducted and showed by using ROS scavengers that ROS production was the triggering factor responsible of atorvastatin-induced activation of mitochondrial biogenesis pathway and improvement of antioxidant capacities in heart. Conversely, in skeletal muscle, the large augmentation of ROS production following treatment induced mitochondrial impairments, and reduced mitochondrial biogenesis mechanisms. Quercetin, an antioxidant molecule, was able to counteract skeletal muscle deleterious effects of atorvastatin in rat. CONCLUSION: Our findings identify statins as a new activating factor of cardiac mitochondrial biogenesis and antioxidant capacities, and suggest the importance of ROS/PGC-1 signalling pathway as a key element in regulation of mitochondrial function in cardiac as well as skeletal muscles.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Other studies have shown increased ROS production and decreased antioxidant capacity with statin treatment.
“other studies have shown increased ROS production (3,42) and a decreased antioxidant capacity (3) with statin treatment.”
From Simvastatin Effects on Skeletal Muscle (2013) · cites this paper as [3]
Reduced antioxidant capacity combined with known elevated ROS production makes it plausible that increased apoptosis contributes to muscle pain in statin-treated patients.
“Our findings of significantly reduced antioxidant capacity in combination with the known (3,40) elevated ROS production in the simvastatin-treated patients make it plausible that increased apoptosis could contribute to muscle pain in patients treated with statins.”
From Simvastatin Effects on Skeletal Muscle (2013) · cites this paper as [3]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J. M., Rhee, J., Jäger, S., Handschin, C., Zheng, K., Lin, J., Yang, W., et al. (2006) · Cell · doi:10.1016/j.cell.2006.09.024 · Cited by 2,233 · see citing works
Schulz, T. J., Zarse, K., Voigt, A., Urban, N., Birringer, M., & Ristow, M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.08.011 · Cited by 1,209 · see citing works
Transcriptional control of mitochondrial biogenesis: the central role of PGC-1
Ventura-Clapier, R., Garnier, A., & Veksler, V. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn098 · Cited by 932 · see citing works
Cerivastatin and Reports of Fatal Rhabdomyolysis
Staffa, J. A., Chang, J. T., & Green, L. (2002) · New England Journal of Medicine · doi:10.1056/nejm200202143460721 · Cited by 627 · see citing works
Piantadosi, C. A., Carraway, M. S., Babiker, A., & Suliman, H. B. (2008) · Circulation Research · doi:10.1161/01.res.0000338597.71702.ad · Cited by 580 · see citing works
Statin effects beyond lipid lowering—are they clinically relevant?
Bonetti, P. O. (2003) · European Heart Journal · doi:10.1016/s0195-668x(02)00419-0 · Cited by 524 · see citing works
Stress-Response Hormesis and Aging: “That which Does Not Kill Us Makes Us Stronger”
Gems, D., & Partridge, L. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.01.001 · Cited by 496 · see citing works
Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1α expression.
Wright, D. C., Han, D.-H., Garcia-Roves, P. M., Geiger, P. C., Jones, T. E., & Holloszy, J. O. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m606116200 · Cited by 488 · see citing works
Mitochondrial H + Leak and ROS Generation: An Odd Couple
Brookes, P. S. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.10.016 · Cited by 447 · see citing works
Lelliott, C. J., Medina-Gomez, G., Petrovic, N., Kis, A., Feldmann, H. M., Bjursell, M., Parker, N., Curtis, K., Campbell, M., Hu, P., et al. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040369 · Cited by 280 · see citing works
Toxicity of statins on rat skeletal muscle mitochondria
Kaufmann, P., Török, M., Zahno, A., Waldhauser, K. M., Brecht, K., & Krähenbühl, S. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6235-z · Cited by 263 · see citing works
[41] Flavonoid antioxidants: Rate constants for reactions with oxygen radicals
Bors, W., Michel, C., & Sarán, M. (1994) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(94)34112-5 · Cited by 210 · see citing works
Statins: a new insight into their mechanisms of action and consequent pleiotropic effects.
Jasińska-Stroschein, M., Owczarek, J., & Orszulak–Michalak, D. (2007) · PubMed · Cited by 192 · see citing works
New insights into mechanisms of statin-associated myotoxicity
Sirvent, P., Mercier, J. G., & Lacampagne, A. (2008) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2007.12.010 · Cited by 190 · see citing works
The antioxidant effects of statins
Davignon, J., Jacob, R. F., & Mason, R. P. (2004) · Coronary Artery Disease · doi:10.1097/01.mca.0000131573.31966.34 · Cited by 162 · see citing works
Emerging Concepts and Translational Priorities in Pulmonary Arterial Hypertension
Michelakis, E. D., Wilkins, M. R., & Rabinovitch, M. (2008) · Circulation · doi:10.1161/circulationaha.106.673988 · Cited by 151 · see citing works
Mettauer, B., Zoll, J., Sanchez, H., Lampert, E., Ribera, F., Veksler, V., Bigard, X. A., Matéo, P., Epailly, É., Lonsdorfer, J., et al. (2001) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(01)01460-7 · Cited by 133 · see citing works
Simvastatin Attenuates Oxidant-Induced Mitochondrial Dysfunction in Cardiac Myocytes
Jones, S. P., Teshima, Y., Akao, M., & Marbán, E. (2003) · Circulation Research · doi:10.1161/01.res.0000097262.21507.df · Cited by 124 · see citing works
Simvastatin induces impairment in skeletal muscle while heart is protected
Sirvent, P., Bordenave, S., Vermaelen, M., Roels, B., Vassort, G., Mercier, J., Raynaud, E., & Lacampagne, A. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.10.108 · Cited by 116 · see citing works
Zheng, Z. J., Chen, H., Ke, G., Fan, Y., Zou, H., Sun, X., Gu, Q., Xu, X., & Ho, P. C. P. (2009) · Diabetes · doi:10.2337/db07-1524 · Cited by 114 · see citing works
"That which does not kill us makes us stronger"
LaCroix, A. Z. (2009) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0b013e3181b4bfaa · Cited by 110 · see citing works
Roles of Exercise and Pharmacokinetics in Cerivastatin-Induced Skeletal Muscle Toxicity
Seachrist, J. L., Loi, C., Evans, M. G., Criswell, K. A., & Rothwell, C. E. (2005) · Toxicological Sciences · doi:10.1093/toxsci/kfi305 · Cited by 77 · see citing works
Polymyositis associated with simvastatin
Giordano, N. G., Senesi, M., Mattii, G., Battisti, E., Villanova, M., & Gennari, C. (1997) · The Lancet · doi:10.1016/s0140-6736(05)61628-5 · Cited by 66 · see citing works
Activation of Mitochondrial Biogenesis by Hormesis
Sano, M., & Fukuda, K. (2008) · Circulation Research · doi:10.1161/circresaha.108.189092 · Cited by 65 · see citing works
Neuromuscular Symptoms and Elevated Creatine Kinase after Statin Withdrawal
Echaniz‐Laguna, A., Mohr, M., & Tranchant, C. (2010) · New England Journal of Medicine · doi:10.1056/nejmc0908215 · Cited by 52 · see citing works
Draeger, A., Sánchez-Freire, V., Monastyrskaya, K., Hoppeler, H. H., Mueller, M., Breil, F., Mohaupt, M. G., & Babiychuk, E. B. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.091140 · Cited by 40 · see citing works
Compartmentation of energy metabolism in atrial myocardium of patients undergoing cardiac surgery
Seppet, E., Eimre, M., Peet, N., Paju, K., Orlova, E., Ress, M., K�vask, S., Piirsoo, A., Saks, V. A., Gellerich, F. N., et al. (2005) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-005-3780-y · Cited by 40 · see citing works
Physiological role of free radicals in skeletal muscles
Lecarpentier, Y. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01047.2007 · Cited by 32 · see citing works
Bindoff, L. A. (2003) · European Heart Journal · doi:10.1016/s0195-668x(02)00694-2 · Cited by 29 · see citing works
Wang, W., & Wong, C. (2009) · Journal of Molecular Medicine · doi:10.1007/s00109-009-0561-1 · Cited by 26 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Pleiotropic Effects of Statins on the Cardiovascular System
Oesterle, A., Laufs, U., & Liao, J. K. (2017) · Circulation Research · doi:10.1161/circresaha.116.308537 · Cited by 1,247 · see citing works
García-Sánchez, A., Miranda‐Díaz, A. G., & Cardona-Muñóz, E. G. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/2082145 · Cited by 333 · see citing works
Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma
Chen, X. '., Stewart, E. A., Shelat, A. A., Qu, C., Bahrami, A., Hatley, M. E., Wu, G., Bradley, C. L., McEvoy, J. D., Pappo, A. S., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.11.002 · Cited by 293 · see citing works
Effects of statins on mitochondrial pathways
Mollazadeh, H., Tavana, E., Fanni, G., Bo, S., Banach, M., Pirro, M., von Haehling, S., Jamialahmadi, T., & Sahebkar, A. (2021) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12654 · Cited by 259 · see citing works
Simvastatin Impairs Exercise Training Adaptations
Mikus, C. R., Boyle, L. J., Borengasser, S. J., Oberlin, D. J., Naples, S. P., Fletcher, J. A., Meers, G. M.-E., Ruebel, M. L., Laughlin, M. H., Dellsperger, K. C., et al. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.02.074 · Cited by 244 · see citing works
Local hyperthermia therapy induces browning of white fat and treats obesity
Li, Y., Wang, D., Ping, X., Zhang, Y., Zhang, T., Wang, L., Li, J., Zhao, W., Guo, M., Shen, F., et al. (2022) · Cell · doi:10.1016/j.cell.2022.02.004 · Cited by 220 · see citing works
MitoTimer: A novel tool for monitoring mitochondrial turnover
Hernandez, G., Thornton, C., Stotland, A., Lui, D., Sin, J., Ramil, J., Magee, N., Andres, A., Quarato, G., Carreira, R. S., et al. (2013) · Autophagy · doi:10.4161/auto.26501 · Cited by 187 · see citing works
Pleiotropic effects of statins
Vasnawala, H., Kavalipati, N., Shah, J., & Ramakrishan, A. (2015) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.163106 · Cited by 181 · see citing works
Emerging role of mitophagy in cardiovascular physiology and pathology
Morales, P. E., Arias-Durán, C., Ávalos-Guajardo, Y., Aedo, G., Verdejo, H., Parra, V., & Lavandero, S. (2019) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2019.09.006 · Cited by 178 · see citing works
Intolerance to Statins: Mechanisms and Management
Bitzur, R., Cohen, H., Kamari, Y., & Harats, D. (2013) · Diabetes Care · doi:10.2337/dcs13-2038 · Cited by 178 · see citing works
Gomez-Cabrera, M. C., Salvador-Pascual, A., Cabo, H., Ferrando, B., & Viña, J. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.04.006 · Cited by 172 · see citing works
Sandhir, R., & Mehrotra, A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.11.018 · Cited by 171 · see citing works
Statins: Adverse reactions, oxidative stress and metabolic interactions
Liu, A., Wu, Q., Guo, J., Arés, I., Rodríguez, J.-L., Martínez‐Larrañaga, M., Yuan, Z., Anadón, A., Wang, X., & Martínez, M. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.10.004 · Cited by 168 · see citing works
Reactive Oxygen Species Scavenging Nanomedicine for the Treatment of Ischemic Heart Disease
Zhang, Z., Dalan, R., Hu, Z., Wang, J., Chew, N., Poh, K. K., Tan, R., Soong, T. W., Dai, Y., Ye, L., et al. (2022) · Advanced Materials · doi:10.1002/adma.202202169 · Cited by 174 · see citing works
Simvastatin Effects on Skeletal Muscle
Larsen, S., Stride, N., Hey-Mogensen, M., Hansen, C. N., Bang, L. E., Bundgaard, H., Nielsen, L. B., Helge, J. W., & Dela, F. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.09.036 · Cited by 165 · see citing works
Antioxidant Effects of Statins by Modulating Nrf2 and Nrf2/HO-1 Signaling in Different Diseases
Mansouri, A., Reiner, Ž., Ruscica, M., Tedeschi-Reiner, E., Radbakhsh, S., Ekta, M. B., & Sahebkar, A. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11051313 · Cited by 164 · see citing works
Myotoxicity of statins: Mechanism of action
du Souich, P., Roederer, G. O., & Dufour, R. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.029 · Cited by 162 · see citing works
Mitochondria in vascular disease
Yu, E., Mercer, J. R., & Bennett, M. R. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs111 · Cited by 152 · see citing works
Chronology of mitochondrial and cellular events during skeletal muscle ischemia-reperfusion
Paradis, S., Charles, A., Meyer, A., Lejay, A., Scholey, J. W., Chakfé, N., Zoll, J., & Gény, B. (2016) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00356.2015 · Cited by 145 · see citing works
Mechanisms of statin-associated skeletal muscle-associated symptoms
Bouitbir, J., Sanvee, G. M., Panajatovic, M. V., Singh, F., & Krähenbühl, S. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.03.010 · Cited by 146 · see citing works
The role of mitochondria in statin‐induced myopathy
Apostolopoulou, M., Corsini, A., & Roden, M. (2015) · European Journal of Clinical Investigation · doi:10.1111/eci.12461 · Cited by 142 · see citing works
Statins and Pulmonary Fibrosis: The Potential Role of NLRP3 Inflammasome Activation
Xu, J., Washko, G. R., Nakahira, K., Hatabu, H., Patel, A. S., Fernandez, I. E., Nishino, M., Okajima, Y., Yamashiro, T., Ross, J. C., et al. (2012) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201108-1574oc · Cited by 140 · see citing works
Gouni‐Berthold, I., Berthold, H. K., Huh, J. Y., Berman, R., Spenrath, N., Krone, W., & Mantzoros, C. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072858 · Cited by 132 · see citing works
Dott, W., Mistry, P., WRIGHT, J. A., Cain, K., & Herbert, K. E. (2014) · Redox Biology · doi:10.1016/j.redox.2013.12.028 · Cited by 125 · see citing works
Atorvastatin Induces Mitochondria-Dependent Ferroptosis via the Modulation of Nrf2-xCT/GPx4 Axis
Zhang, Q., Qu, H., Chen, Y., Luo, X., Chen, C., Xiao, B., Ding, X., Zhao, P., Lu, Y., Chen, A. F., et al. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.806081 · Cited by 116 · see citing works
A new therapeutic effect of simvastatin revealed by functional improvement in muscular dystrophy
Whitehead, N. P., Kim, M. J., Bible, K. L., Adams, M. E., & Froehner, S. C. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1509536112 · Cited by 111 · see citing works
Mechanisms of Hepatocellular Toxicity Associated with Dronedarone—A Comparison to Amiodarone
Felser, A., Blum, K., Lindinger, P. W., Bouitbir, J., & Krähenbühl, S. (2012) · Toxicological Sciences · doi:10.1093/toxsci/kfs298 · Cited by 109 · see citing works
Li, X., Wang, H., Gao, Y., Li, L., Tang, C., Wen, G., Zhou, Y., Zhou, M., Mao, L., & Fan, Y. (2016) · PLoS ONE · doi:10.1371/journal.pone.0164237 · Cited by 109 · see citing works
Reductive stress impairs myoblasts mitochondrial function and triggers mitochondrial hormesis
Singh, F., Charles, A., Schlagowski, A.-I., Bouitbir, J., Bonifacio, A., Piquard, F., Krähenbühl, S., Gény, B., & Zoll, J. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.03.006 · Cited by 104 · see citing works
Role of PGC-1α in Vascular Regulation
Kadlec, A. O., Chabowski, D. S., Ait‐Aissa, K., & Gutterman, D. D. (2016) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.116.307123 · Cited by 102 · see citing works
Statins, Muscle Disease and Mitochondria
Ramachandran, R., & Wierzbicki, A. S. (2017) · Journal of Clinical Medicine · doi:10.3390/jcm6080075 · Cited by 91 · see citing works
The AKT/mTOR signaling pathway plays a key role in statin-induced myotoxicity
Bonifacio, A., Sanvee, G. M., Bouitbir, J., & Krähenbühl, S. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.04.010 · Cited by 93 · see citing works
Bouitbir, J., Singh, F., Charles, A., Schlagowski, A.-I., Bonifacio, A., Echaniz‐Laguna, A., Gény, B., Krähenbühl, S., & Zoll, J. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.6190 · Cited by 95 · see citing works
Human Skeletal Muscle Mitochondrial Adaptations Following Resistance Exercise Training
Parry, H. A., Roberts, M. D., & Kavazis, A. N. (2020) · International Journal of Sports Medicine · doi:10.1055/a-1121-7851 · Cited by 92 · see citing works
Pharmacological Strategies to Retard Cardiovascular Aging
Alfaras, I., Germanio, C. D., Bernier, M., Csiszár, A., Ungvari, Z. I., Lakatta, E. G., & de Cabo, R. (2016) · Circulation Research · doi:10.1161/circresaha.116.307475 · Cited by 87 · see citing works
Rasmussen, S. T., Andersen, J. T., Nielsen, T. K., Cejvanovic, V., Petersen, K. M., Henriksen, T., Weimann, A., Lykkesfeldt, J., & Poulsen, H. E. (2016) · Redox Biology · doi:10.1016/j.redox.2016.05.007 · Cited by 85 · see citing works
Muntean, D. M., Thompson, P. D., Catapano, A. L., Stasiolek, M., Fabis, J., Muntner, P., Serban, M.-C., & Banach, M. (2017) · Drug Discovery Today · doi:10.1016/j.drudis.2016.09.001 · Cited by 82 · see citing works
New and revisited approaches to preserving the reperfused myocardium
Kloner, R. A., Brown, D. A., CSETE, M. E., Dai, W., Downey, J. M., Gottlieb, R. A., Hale, S. L., & Shi, J. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.102 · Cited by 83 · see citing works
Wu, F., Li, Z., Cai, M., Xi, Y., Xu, Z., Zhang, Z., Li, H., Zhu, W., & Tian, Z. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.06.038 · Cited by 83 · see citing works
Mitochondrial Function and Dysfunction: An Update
Davis, R. E., & Williams, M. J. (2012) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.192104 · Cited by 83 · see citing works
Bland, A. R., Payne, F. M., Ashton, J. C., Jamialahmadi, T., & Sahebkar, A. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105986 · Cited by 82 · see citing works
Drug induced mitochondrial dysfunction: Mechanisms and adverse clinical consequences
Vuda, M., & Kamath, A. (2016) · Mitochondrion · doi:10.1016/j.mito.2016.10.005 · Cited by 83 · see citing works
Meyer, A., Zoll, J., Charles, A. L., Charloux, A., de Blay, F., Diemunsch, P., Sibilia, J., Piquard, F., & Geny, B. (2013) · Experimental Physiology · doi:10.1113/expphysiol.2012.069468 · Cited by 90 · see citing works
Decreased skeletal muscle mitochondrial DNA in patients with statin-induced myopathy
Stringer, H. A. J., Sohi, G. K., Maguire, J. A., & Côté, H. C. F. (2013) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2012.12.023 · Cited by 79 · see citing works
Urbano, F., Bugliani, M., Filippello, A., Scamporrino, A., Mauro, S. D., Pino, A. D., Scicali, R., Noto, D., Rabuazzo, A. M., Averna, M. R., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-11070-x · Cited by 78 · see citing works
Molecular mechanisms of statin intolerance
Gluba-Brzózka, A., Franczyk, B., Toth, P. P., Rysz, J., & Banach, M. (2016) · Archives of Medical Science · doi:10.5114/aoms.2016.59938 · Cited by 73 · see citing works
Atherosclerosis and the Capillary Network; Pathophysiology and Potential Therapeutic Strategies
Ziegler, T., Rahman, F. A., Jurisch, V., & Kupatt, C. (2019) · Cells · doi:10.3390/cells9010050 · Cited by 74 · see citing works
Pal, S., Ghosh, M., Ghosh, S., Bhattacharyya, S., & Sil, P. C. (2015) · Food and Chemical Toxicology · doi:10.1016/j.fct.2015.05.016 · Cited by 72 · see citing works
Aging Fits the Disease Criteria of the International Classification of Diseases
Khaltourina, D. A., Matveyev, Y., Alekseev, A., Cortese, F., & Ioviţă, A. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111230 · Cited by 71 · see citing works
Mitochondrial oxidative stress plays a critical role in the cardiotoxicity of sunitinib
Bouitbir, J., Alshaikhali, A., Panajatovic, M. V., Abegg, V. F., Paech, F., & Krähenbühl, S. (2019) · Toxicology · doi:10.1016/j.tox.2019.152281 · Cited by 68 · see citing works
Statins and skeletal muscles toxicity: From clinical trials to everyday practice
Norata, G. D., Tibolla, G., & Catapano, A. L. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.04.012 · Cited by 64 · see citing works
Bonifacio, A., Mullen, P. J., Mityko, I. S., Navegantes, L. C. C., Bouitbir, J., & Krähenbühl, S. (2014) · Archives of Toxicology · doi:10.1007/s00204-014-1378-4 · Cited by 61 · see citing works
Charles, A., Guilbert, A.-S., Guillot, M., Talha, S., Lejay, A., Meyer, A., Kindo, M., Wolff, V., Bouitbir, J., Zoll, J., et al. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00052 · Cited by 56 · see citing works
Vaughan, R. A., Garcia-Smith, R., Bisoffi, M., Conn, C. A., & Trujillo, K. A. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.04.009 · Cited by 58 · see citing works
Ahmed, L. A., Darwish, H. A., Abdelsalam, R. M., & Amin, H. A. (2016) · Molecular Neurobiology · doi:10.1007/s12035-015-9303-2 · Cited by 55 · see citing works
Mansour, Z., Bouitbir, J., Charles, A. L., Talha, S., Kindo, M. J., Pottecher, J., Zoll, J., & Gény, B. (2011) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2011.07.084 · Cited by 55 · see citing works
Marcheggiani, F., Cirilli, I., Orlando, P., Silvestri, S., Vogelsang, A., Knott, A., Blatt, T., Weise, J. M., & Tiano, L. (2019) · Aging · doi:10.18632/aging.101926 · Cited by 53 · see citing works
A Mechanism for Statin-Induced Susceptibility to Myopathy
Lotteau, S. J., Ivarsson, N., Yang, Z., Restagno, D., Colyer, J., Hopkins, P. M., Weightman, A., Himori, K., Yamada, T., Bruton, J. D., et al. (2019) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2019.03.012 · Cited by 54 · see citing works
Charles, A., Meyer, A., Dal-Ros, S., Auger, C., Keller, N., Ramamoorthy, T. G., Zoll, J., METZGER, D., Schini‐Kerth, V. B., & Gény, B. (2012) · Experimental Physiology · doi:10.1113/expphysiol.2012.067496 · Cited by 53 · see citing works
Enache, I., Charles, A., Bouitbir, J., Favret, F., Zoll, J., METZGER, D., Oswald–Mammosser, M., Gény, B., & Charloux, A. (2012) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-012-1485-6 · Cited by 53 · see citing works
Egom, E. E. A., & Hafeez, H. (2016) · Advances in clinical chemistry · doi:10.1016/bs.acc.2015.10.005 · Cited by 54 · see citing works
Li, F., Wang, X., Deng, Z.-K., Zhang, X., Gao, P., & Liu, H. (2018) · Neuropeptides · doi:10.1016/j.npep.2018.10.004 · Cited by 53 · see citing works
Mitochondrial Dysfunction, Oxidative Stress and Diabetic Cardiovascular Disorders
Shen, G. X. (2012) · Cardiovascular & Haematological Disorders - Drug Targets · doi:10.2174/1871529x11202020106 · Cited by 50 · see citing works
Iron, Oxidative Damage and Ferroptosis in Rhabdomyosarcoma
Fanzani, A., & Poli, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18081718 · Cited by 50 · see citing works
Targeting of stress response pathways in the prevention and treatment of cancer
Zelenka, J., Koncošová, M., & Ruml, T. (2018) · Biotechnology Advances · doi:10.1016/j.biotechadv.2018.01.007 · Cited by 50 · see citing works
Heart failure with preserved ejection fraction: Defining the function of ROS and NO
Zuo, L., Chuang, C., Hemmelgarn, B. T., & Best, T. M. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01149.2014 · Cited by 48 · see citing works
Mitochondria of trained skeletal muscle are protected from deleterious effects of statins
Bouitbir, J., Daussin, F., Charles, A., Rasseneur, L., Dufour, S. P., Richard, R., Piquard, F., Gény, B., & Zoll, J. (2012) · Muscle & Nerve · doi:10.1002/mus.23309 · Cited by 46 · see citing works
Guardia, P. G. L., Alberici, L. C., Ravagnani, F. G., Catharino, R. R., & Vercesi, A. E. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00103 · Cited by 46 · see citing works
Mechanisms of hepatotoxicity associated with the monocyclic β-lactam antibiotic BAL30072
Paech, F., Messner, S., Spickermann, J., Wind, M., Schmitt-Hoffmann, A.-H., Witschi, A. T., Howell, B. A., Church, R. J., Woodhead, J., Engelhardt, M. F., et al. (2017) · Archives of Toxicology · doi:10.1007/s00204-017-1994-x · Cited by 45 · see citing works
The effects of statins on exercise and physical activity
Noyes, A. M., & Thompson, P. D. (2017) · Journal of clinical lipidology · doi:10.1016/j.jacl.2017.07.003 · Cited by 44 · see citing works
Cao, L., Li, Y. S., Smirnov, A., Voshtani, R., Wang, T., Shao, C., Candi, E., Melino, G., Shi, Y., & Fang, J. (2025) · Cell & Bioscience · doi:10.1186/s13578-025-01519-2 · Cited by 48 · see citing works
Dohlmann, T. L., Morville, T. H., Kuhlman, A. B., Chrøis, K. M., Helge, J. W., Dela, F., & Larsen, S. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01185 · Cited by 44 · see citing works
Mechanisms of simvastatin myotoxicity: The role of autophagy flux inhibition
Emami, A., Shojaei, S., Rosa, S. C. D. S., Aghaei, M., Samiei, E., Vosoughi, A. R., Kalantari, F., Kawalec, P., Thliveris, J. A., Sharma, P. K., et al. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.172616 · Cited by 42 · see citing works
Pal, S., Sarkar, A., Pal, P. B., & Sil, P. C. (2015) · Biochimie · doi:10.1016/j.biochi.2015.02.016 · Cited by 40 · see citing works
Wang, L., Zhang, X., Chan, J. Y., Shan, L., Cui, G., Cui, Q., Wang, Y., Li, J., Chen, H., Zhang, Q., et al. (2015) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25253 · Cited by 38 · see citing works
Vilne, B., Skogsberg, J., Asl, H. F., Talukdar, H. A., Kessler, T., Björkegren, J., & Schunkert, H. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.10.019 · Cited by 36 · see citing works
Goodman, C. A., Derk, P., Zacharewicz, E., Lee, R. S., Snow, R. J., Russell, A. P., & McConell, G. K. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128398 · Cited by 35 · see citing works
Baratli, Y., Charles, A., Wolff, V., Tahar, L. B., Smiri, L. S., Bouitbir, J., Zoll, J., Piquard, F., Tebourbi, O., Sakly, M., et al. (2013) · Toxicology in Vitro · doi:10.1016/j.tiv.2013.09.006 · Cited by 35 · see citing works
Kindo, M. J., Gerelli, S., Bouitbir, J., Charles, A., Zoll, J., Minh, T. H., Monassier, L., Favret, F., Piquard, F., & Gény, B. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00332 · Cited by 35 · see citing works
Vaughan, R. A., Mermier, C. M., Bisoffi, M., Trujillo, K. A., & Conn, C. A. (2014) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-013-0301-4 · Cited by 34 · see citing works
Guo, Z., Tian, Y., Liu, N., Chen, Y., Chen, X., Yuan, G., Chang, A., Chang, X., Wu, J., & Zhou, H. (2024) · International Journal of Medical Sciences · doi:10.7150/ijms.99359 · Cited by 34 · see citing works
Malboosi, N., Nasehi, M., Hashemi, M., Vaseghi, S., & Zarrindast, M. (2020) · Gene · doi:10.1016/j.gene.2020.144601 · Cited by 34 · see citing works
Maarman, G. J. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-63245-2_10 · Cited by 33 · see citing works
Bennett, N. K., Lee, M., Orr, A. L., & Nakamura, K. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2307904121 · Cited by 32 · see citing works
The Effects of Statin Medications on Aerobic Exercise Capacity and Training Adaptations
Murlasits, Z., & Radak, Z. O. (2014) · Sports Medicine · doi:10.1007/s40279-014-0224-4 · Cited by 32 · see citing works
IGF-1 prevents simvastatin-induced myotoxicity in C2C12 myotubes
Bonifacio, A., Sanvee, G. M., Brecht, K., Kratschmar, D. V., Odermatt, A., Bouitbir, J., & Krähenbühl, S. (2016) · Archives of Toxicology · doi:10.1007/s00204-016-1871-z · Cited by 31 · see citing works
Fernandes, M., Patel, A., & Husi, H. (2018) · PLoS ONE · doi:10.1371/journal.pone.0207371 · Cited by 31 · see citing works
Nasehi, M., Torabinejad, S., Hashemi, M., Vaseghi, S., & Zarrindast, M. (2019) · Metabolic Brain Disease · doi:10.1007/s11011-019-00508-y · Cited by 30 · see citing works
Pathogenic Implications of Human Mitochondrial Aminoacyl-tRNA Synthetases
Schwenzer, H., Zoll, J., Florentz, C., & Sissler, M. (2013) · Topics in current chemistry · doi:10.1007/128_2013_457 · Cited by 30 · see citing works
Shi, Z., & Han, S. (2025) · Heliyon · doi:10.1016/j.heliyon.2025.e41629 · Cited by 34 · see citing works
The mitohormetic response as part of the cytoprotection mechanism of berberine
Zhu, X., Wei, Y., Yang, B., Yin, X., & Guo, X. (2020) · Molecular Medicine · doi:10.1186/s10020-020-0136-8 · Cited by 28 · see citing works
Effects of statins on myocarditis: A review of underlying molecular mechanisms
Parsamanesh, N., Karami‐Zarandi, M., Banach, M., Penson, P. E., & Sahebkar, A. (2021) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2021.02.008 · Cited by 28 · see citing works
Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail?
Nsaibia, M. J., Devendran, A. S., Goubaa, E., Bouitbir, J., Capoulade, R., & Bouchareb, R. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11123331 · Cited by 24 · see citing works
Feng, H., Wang, J., Zheng, M., Zhang, C., An, Y., Li, L., & Wu, L. (2016) · Experimental Cell Research · doi:10.1016/j.yexcr.2016.02.001 · Cited by 25 · see citing works
CYP2J2 Expression in Adult Ventricular Myocytes Protects Against Reactive Oxygen Species Toxicity
Evangelista, E. A., Lemaître, R. N., Sotoodehnia, N., Gharib, S. A., & Totah, R. A. (2018) · Drug Metabolism and Disposition · doi:10.1124/dmd.117.078840 · Cited by 27 · see citing works
Katsiki, N., Mikhailidis, D. P., Bajraktari, G., Miserez, A. R., Cicero, A. F. G., Bruckert, É., Șerban, M.-C., Mirrakhimov, E. M., Alnouri, F., Reiner, Ž., et al. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104719 · Cited by 27 · see citing works
Dohlmann, T. L., Kuhlman, A. B., Morville, T., Dahl, M., Asping, M., Orlando, P., Silvestri, S., Tiano, L., Helge, J. W., Dela, F., et al. (2022) · Antioxidants · doi:10.3390/antiox11091698 · Cited by 31 · see citing works
Inflammatory Stress Sensitizes the Liver to Atorvastatin-Induced Injury in ApoE-/- Mice
Wu, W., Zhao, L., Yang, P., Zhou, W., Li, B., Moorhead, J. F., Varghese, Z., Ruan, X. Z., & Chen, Y. (2016) · PLoS ONE · doi:10.1371/journal.pone.0159512 · Cited by 25 · see citing works
Ren, L., Xuan, L., Han, F., Zhang, J., Gong, L., Lv, Y., Zhang, W., Yang, S. T., Xu, B., Yan, Y., et al. (2020) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2020.115076 · Cited by 25 · see citing works
Pleiotropic Benefits of Statins in Cardiovascular Diseases
Wasim, R., Ansari, T. M., Ahsan, F., Siddiqui, M. H., Singh, A., Shariq, M., & Parveen, S. (2022) · Drug Research · doi:10.1055/a-1873-1978 · Cited by 23 · see citing works
- Authors
- Bouitbir, J., Charles, A.-L., Echaniz-Laguna, A., Kindo, M., Daussin, F., Auwerx, J., Piquard, F., Geny, B., & Zoll, J.
- Affiliations
- Hôpital Civil, Strasbourg (FR)
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Zoll, Joffrey
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-07-20
- Volume
- 33
- Issue
- 11
- Pages
- 1397-1407
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- PMC
- PMC3365271
- OpenAlex
- W2102743559
- Cited by
- 256
- References
- 30
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 13 · 2023: 14 · 2022: 18 · 2021: 12 · 2020: 24 · 2019: 22 · 2018: 18 · 2017: 22 · 2016: 25 · 2015: 18 · 2014: 9 · 2013: 17 · 2012: 16
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Heart Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- HAL (submittedVersion)
- edoc (University of Basel) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- National Science Foundation
- Institut National de la Santé et de la Recherche Médicale
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-59820, P01DK059820)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- statins, atorvastatin, statin-induced myopathy, heart mitochondria, skeletal muscle mitochondria, reactive oxygen species, PGC-1, mitochondrial biogenesis, oxidative stress, antioxidant capacity, quercetin, mitohormesis, cardioprotection
- MeSH terms
- Atorvastatin, Animals, Antioxidants, Heart Atria, Heptanoic Acids, Humans, Male, Mitochondria, Heart, Mitochondria, Muscle, Pyrroles, Quercetin, RNA, Messenger, Superoxide Dismutase, Transcription Factors, Rats, Wistar, Reactive Oxygen Species, Muscle, Skeletal, Muscle Fibers, Skeletal, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Myocytes, Cardiac, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
