ArticleAntioxidants & redox signaling2014
Mitophagy is required for acute cardioprotection by simvastatin.
Article in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 188 citations in OpenAlex.
- Phase I/IIa Trial of Atorvastatin in Patients with Acute Kawasaki Disease with Coronary Artery Aneurysm.The Journal of pediatrics · 2019Trial
- Trial
- Reversing diastolic dysfunction in diabetes: a mitochondrial quality control-centric pharmacological approach.Acta diabetologica · 2026Review
- Pharmacological reactivation of autophagic flux by natural compounds or synthetic cell-permeable peptide prevents doxorubicin-induced cardiomyopathy.Basic research in cardiology · 2026Article
- Role of mitophagy in acute and fractionated gamma radiation-induced nephropathy in rats: insight into molecular biology and repurposing of rosuvastatin.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Regulatory mechanisms and interactions of mitophagy and ketone body metabolism in cardiac metabolism.Frontiers in cardiovascular medicine · 2026Review
- Increased Risk of Myocardial Infarction in Inclusion Body Myositis: A Non-Concurrent Cohort Study.European journal of neurology · 2025Article
- Enhanced Parkin-mediated mitophagy mitigates adverse left ventricular remodelling after myocardial infarction: role of PR-364.European heart journal · 2025Article
- Cardioprotective Effects of Adiponectin-Stimulated Autophagy.Journal of lipid and atherosclerosis · 2025Review
- Dysregulated RBM24 phosphorylation impairs APOE translation underlying psychological stress-induced cardiovascular disease.Nature communications · 2024Article
- Crosstalk among Reactive Oxygen Species, Autophagy and Metabolism in Myocardial Ischemia and Reperfusion Stages.Aging and disease · 2024Review
- Pachyonychia Congenita: A Research Agenda Leading to New Therapeutic Approaches.The Journal of investigative dermatology · 2024Review
- Therapeutic Strategies Targeting Mitochondrial Dysfunction in Sepsis-induced Cardiomyopathy.Cardiovascular drugs and therapy · 2024Review
- Crosstalk between myocardial autophagy and sterile inflammation in the development of heart failure.Autophagy reports · 2024Review
- Mitochondrial Stress as a Central Player in the Pathogenesis of Hypoxia-Related Myocardial Dysfunction: New Insights.International journal of medical sciences · 2024Review
- Methods for detection of cardiac glycogen-autophagy.Autophagy reports · 2024Article
- Mitochondrial Fission as a Therapeutic Target for Metabolic Diseases: Insights into Antioxidant Strategies.Antioxidants (Basel, Switzerland) · 2023Review
- Mitochondrial Dysfunction in the Cardio-Renal Axis.International journal of molecular sciences · 2023Review
- Mitophagy as a mitochondrial quality control mechanism in myocardial ischemic stress: from bench to bedside.Cell stress & chaperones · 2023Review
- An AI-guided screen identifies probucol as an enhancer of mitophagy through modulation of lipid droplets.PLoS biology · 2023Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
aimsWe have shown that autophagy and mitophagy are required for preconditioning. While statin's cardioprotective effects are well known, the role of autophagy/mitophagy in statin-mediated cardioprotection is not. In this study, we used HL-1 cardiomyocytes and mice subjected to ischemia/reperfusion to elucidate the mechanism of statin-mediated cardioprotection.
resultsHL-1 cardiomyocytes exposed to simvastatin for 24 h exhibited diminished protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling, increased activation of unc-51-like kinase 1, and upregulation of autophagy and mitophagy. Similar findings were obtained in hearts of mice given simvastatin. Mevalonate abolished simvastatin's effects on Akt/mTOR signaling and autophagy induction in HL-1 cells, indicating that the effects are mediated through inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Simvastatin-treated HL-1 cells exhibited mitochondrial translocation of Parkin and p62/SQSTM1, fission, and mitophagy. Because Parkin is required for mitophagy and is expressed in heart, we investigated the effect of simvastatin on infarct size in Parkin knockout mice. Simvastatin reduced infarct size in wild-type mice but showed no benefit in Parkin knockout mice. Inhibition of HMG-CoA reductase limits mevalonate availability for both cholesterol and coenzyme Q10 (CoQ) biosynthesis. CoQ supplementation had no effect on statin-induced Akt/mTOR dephosphorylation or macroautophagy in HL-1 cells, but it potently blocked mitophagy. Importantly, CoQ supplementation abolished statin-mediated cardioprotection in vivo. INNOVATION AND
conclusionAcute simvastatin treatment suppresses mTOR signaling and triggers Parkin-dependent mitophagy, the latter which is required for cardioprotection. Coadministration of CoQ with simvastatin impairs mitophagy and cardioprotection. These results raise the concern that CoQ may interfere with anti-ischemic benefits of statins mediated through stimulation of mitophagy.
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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.