ArticleJCI insight2024
Enhancing mitochondrial pyruvate metabolism ameliorates ischemic reperfusion injury in the heart.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Lactylation: Metabolic epigenetic regulation and cell death mechanisms in myocardial ischemia‒reperfusion injury.Genes & diseases · 2027Review
- Review
- The mtROS-Mitophagy Axis: A Decisive Redox Hub Governing Cell Fate in Myocardial Ischemia-Reperfusion Injury.Cardiovascular toxicology · 2026Review
- Reverse engineering of BNIP3 identifies a mitochondrial protective peptide.Nature communications · 2026Article
- Lactylation in cardiac repair: Nexus and therapeutic opportunity.Journal of molecular and cellular cardiology plus · 2026Review
- Metabolic inflexibility across heart failure phenotypes: mechanisms and type-specific therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Review
- FABP5 confers resistance to drug-induced ROS toxicity in cervical cancer cell lines by suppressing the PPARγ/CPT1A signaling pathway.Discover oncology · 2026Article
- [3-Npj imaging · 2026Article
- Tricarboxylic acid cycle metabolite index predicts adverse outcomes in acute myocardial infarction patients.BMC medicine · 2026Article
- Dual role of lactate in ferroptosis: Mechanisms, pathophysiology and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Untargeted metabolomics-based elucidation of metabolic reprogramming mechanisms and pathways following aortic dissection surgery.European journal of medical research · 2025Article
- Adenosine triphosphate-induced cell death in heart failure: Is there a link?World journal of cardiology · 2025Review
- Leptin drives glucose metabolism to promote cardiac protection via OPA1-mediated HDAC5 translocation and Glut4 transcription.Functional & integrative genomics · 2025Article
- Impact of evidence-based nursing interventions on psychological status and myocardial injury in patients with myocardial infarction following percutaneous coronary intervention for reperfusion injury.Frontiers in physiology · 2025Article
- Characterization of protein lactylation in healthy and ischemic mouse hearts.Frontiers in cardiovascular medicine · 2025Article
- Integrative Analysis Reveals a Key Role for CDKN1A in Impaired Wound Healing in Diabetic Patients.Clinical, cosmetic and investigational dermatology · 2025Article
- Plasma Levels of Propionylcarnitine Improved Prediction of Heart Failure and All-Cause Mortality in Patients with Stable Coronary Artery Disease.Biomolecules · 2024Article
- Direct mitochondrial import of lactate supports resilient carbohydrate oxidation.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
- Erratum issued
- Update of
Authors and funding
17 authors.
Funding
Abstract
The clinical therapy for treating acute myocardial infarction is primary percutaneous coronary intervention (PPCI). PPCI is effective at reperfusing the heart; however, the rapid reintroduction of blood can cause ischemia-reperfusion (I/R). Reperfusion injury is responsible for up to half of the total myocardial damage, but there are no pharmacological interventions to reduce I/R. We previously demonstrated that inhibiting monocarboxylate transporter 4 (MCT4) and redirecting pyruvate toward oxidation can blunt hypertrophy. We hypothesized that this pathway might be important during I/R. Here, we establish that the pyruvate-lactate axis plays a role in determining myocardial salvage following injury. After I/R, the mitochondrial pyruvate carrier (MPC), required for pyruvate oxidation, is upregulated in the surviving myocardium. In cardiomyocytes lacking the MPC, there was increased cell death and less salvage after I/R, which was associated with an upregulation of MCT4. To determine the importance of pyruvate oxidation, we inhibited MCT4 with a small-molecule drug (VB124) at reperfusion. This strategy normalized reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨ), and Ca2+, increased pyruvate entry to the TCA cycle, increased oxygen consumption, and improved myocardial salvage and functional outcomes following I/R. Our data suggest normalizing pyruvate-lactate metabolism by inhibiting MCT4 is a promising therapy to mitigate I/R injury.
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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.