ArticleEuropean heart journal2012
Opposite effects of statins on mitochondria of cardiac and skeletal muscles: a 'mitohormesis' mechanism involving reactive oxygen species and PGC-1.
Article in European heart journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 247 citations in OpenAlex.
- The effects of 2 weeks of statin treatment on mitochondrial respiratory capacity in middle-aged males: the LIFESTAT study.European journal of clinical pharmacology · 2017Trial
- Simvastatin and oxidative stress in humans: A randomized, double-blinded, placebo-controlled clinical trial.Redox biology · 2016Trial
- Simvastatin impairs exercise training adaptations.Journal of the American College of Cardiology · 2013 · on this mapTrial
- Effects of lipid-lowering drugs on irisin in human subjects in vivo and in human skeletal muscle cells ex vivo.PloS one · 2013Trial
- Mitochondrial superoxide-induced mitohormesis is mediated by citrate and cardioprotective.Science advances · 2026Article
- Statin Therapy and Cardiovascular Prevention: Contemporary Evidence, Challenges, and Future Directions-A Narrative Review.International journal of environmental research and public health · 2026Review
- Metformin Partially Attenuates Simvastatin-Induced Myotoxic Responses in C2C12 Myotubes Through Metabolic Adaptation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Statin-Induced Coenzyme Q Deficiency Induces Metabolic Reprogramming in Astrocytes.Antioxidants (Basel, Switzerland) · 2026Article
- Comparison of seprafilm and pitavastatin treatments in an experimental model of peritoneal adhesion.Scientific reports · 2026Article
- Thymoquinone protects against statin-induced cerebellar damage, apoptosis, and hepatic cytotoxicity in rats.Scientific reports · 2026Article
- Cardiovascular Effects of Early and Postponed Statin Treatment After Ovariectomy in Prediabetic Rat.Physiological research · 2026Article
- PGC-1α: key regulator of mitochondrial biogenesis and cellular differentiation in metabolic and regenerative tissues.Cell & bioscience · 2025Review
- Targeting TOMM40 and TOMM22 to Rescue Statin-Impaired Mitochondrial Function, Dynamics, and Mitophagy in Skeletal Myotubes.International journal of molecular sciences · 2025Article
- Investigation into the synergistic effect of atorvastatin combined with ultrasound stimulation for anti-glioma therapy.Oncology letters · 2025Article
- Effects of HMG CoA reductase (HMGCR) deficiency on skeletal muscle development.The FEBS journal · 2025Article
- Evaluation of the toxicity potential of exercise and atorvastatin/metformin combination therapy on STZ-diabetic rats.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Cerebral Small Vessel Disease: Therapeutic Approaches Targeting Neuroinflammation, Oxidative Stress, and Endothelial Dysfunction.Current issues in molecular biology · 2025Review
- Personalized statin therapy: Targeting metabolic processes to modulate the therapeutic and adverse effects of statins.Heliyon · 2025Review
- Dietary resveratrol improves semen quality by promoting mitochondrial function-related genes expression in aging boars.Journal of animal science · 2025Article
- Enhancing the human health and lifespan: a targeted strategy emphasizing statins.Biogerontology · 2024Review
49 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
aimsStatins 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
resultsIn 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.
conclusionOur 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.