ArticleMetabolism: clinical and experimental2016
The protective effect of trimetazidine on myocardial ischemia/reperfusion injury through activating AMPK and ERK signaling pathway.
Article in Metabolism: clinical and experimental, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Pooled it
- Early Trimetazidine Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST Segment Elevation Myocardial Infarction Reduces Myocardial Infarction Size.Cardiovascular drugs and therapy · 2023Trial
- [Effect of trimetazidine on cardiac function and exercise tolerance in hypertension patients with diabetic].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2019Trial
- Coenzyme Q10 combined with trimetazidine in the prevention of contrast-induced nephropathy in patients with coronary heart disease complicated with renal dysfunction undergoing elective cardiac catheterization: a randomized control study and in vivo study.European journal of medical research · 2018Trial
- Nanocarrier-Based Therapeutic Strategies in Myocardial Ischemia-Reperfusion Injury: A Systematic Review of Preclinical Evidence.Biomedicines · 2026Review
- An international, double-blind, randomized, placebo-controlled clinical trial of adjunctive trimetazidine to treat people with bipolar depression (the TIDE trial) protocol.BMC psychiatry · 2026Article
- Dexmedetomidine Blocks the ERK Pathway by Inhibiting MAP3K8 to Achieve a Protective Effect in Lung Ischemia/Reperfusion Injury.The Kaohsiung journal of medical sciences · 2025Article
- Irisin regulates cardiac myocyte energy metabolic remodeling involved the ADRA1A-AMPK signaling pathwayng pathway.European journal of medical research · 2025Article
- Trimetazidine in Cardiovascular Disease and Beyond: A Comprehensive Review.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2025Review
- Cardioprotective strategies in myocardial ischemia-reperfusion injury: Implications for improving clinical translation.Journal of molecular and cellular cardiology plus · 2025Review
- Cardiomyocytes in Hypoxia: Cellular Responses and Implications for Cell-Based Cardiac Regenerative Therapies.Bioengineering (Basel, Switzerland) · 2025Review
- Metabolomics in Atrial Fibrillation: Unlocking Novel Biomarkers and Pathways for Diagnosis, Prognosis, and Personalized Treatment.Journal of clinical medicine · 2024Review
- N-Terminomic Identification of Intracellular MMP-2 Substrates in Cardiac Tissue.Journal of proteome research · 2024Article
- Crosstalk among Reactive Oxygen Species, Autophagy and Metabolism in Myocardial Ischemia and Reperfusion Stages.Aging and disease · 2024Review
- Mitochondrial Kinase Signaling for Cardioprotection.International journal of molecular sciences · 2024Review
- Biochemical Aspects That Lead to Abusive Use of Trimetazidine in Performance Athletes: A Mini-Review.International journal of molecular sciences · 2024Review
- Integrated multi-omics approach revealed TTNtv c.13254T>G causing dilated cardiomyopathy in mice.PloS one · 2024Article
- Regulatory effects of trimetazidine in cardiac ischemia/reperfusion injury.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine.Molecular psychiatry · 2023Review
- The role of (Diagnostic and interventional radiology (Ankara, Turkey) · 2023Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
introductionTrimetazidine (TMZ) is an anti-anginal drug that has been widely used in Europe and Asia. The TMZ can optimize energy metabolism via inhibition of long-chain 3-ketoacyl CoA thiolase (3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. However, the mechanism by which TMZ aids in cardioprotection against ischemic injury has not been characterized. AMP-activated protein kinase (AMPK) is an energy sensor that controls ATP supply from substrate metabolism and protects heart from energy stress. TMZ changes the cardiac AMP/ATP ratio by modulating fatty acid oxidation, thereby triggering AMPK signaling cascade that contributes to the protection of the heart from ischemia/reperfusion (I/R) injury.
methodsThe mouse model of in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery (LAD) was used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead (KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart.
resultsTMZ treatment significantly stimulates cardiac AMPK and extracellular signal-regulated kinase (ERK) signaling pathways (p<0.05 vs. vehicle group). The administration of TMZ reduces myocardial infarction size in WT C57BL/6J hearts, the reduction of myocardial infarction size by TMZ in AMPK KD hearts was significantly impaired versus WT hearts (p<0.05). Intriguingly, the administration of ERK inhibitor, PD98059, to AMPK KD mice abolished the cardioprotection of TMZ against I/R injury. The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Therefore, both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. The metabolic benefits of TMZ for angina patients could be due to the activation of energy sensor AMPK in the heart by TMZ administration.
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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.