ArticleCirculation2024
Transient Inhibition of Translation Improves Cardiac Function After Ischemia/Reperfusion by Attenuating the Inflammatory Response.
Article in Circulation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Development of a protein synthesis network at the sarco/endoplasmic reticulum in adult cardiac myocytes.The Journal of physiology · 2026Article
- Biomimetic Bone Marrow Monocyte Membrane-Fused Extracellular Vesicles for Targeted Therapy of Myocardial Infarction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cellular Senescence and the SASP in HFpEF: Pathogenic Mechanisms and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- RMC-6272, a selective third-generation bi-steric mTORC1 inhibitor, improves cardiac function in pressure overload-induced cardiac hypertrophy.Journal of molecular and cellular cardiology plus · 2026Article
- A Post-GWAS Analysis of the Shared Genetic Architecture Between COVID-19 and Coronary Artery Disease.International journal of molecular sciences · 2026Article
- 4E-BP inhibition ameliorates heart failure through translational upregulation of SERCA2a and modulation of mitochondrial redox signaling in cardiomyocytes.Redox biology · 2026Article
- Comprehensive analysis of aberrant alternative splicing and RNA binding proteins regulators associated with myocardial ischemia reperfusion injury in mice.Scientific reports · 2026Article
- Early Postreperfusion Proteomics Reveal Divergent Inflammatory Responses in Kidney Transplantation With Implications on Outcomes.Transplantation · 2026Article
- ALKBH3 suppresses ischemia/reperfusion-induced PANoptosis by regulating the ZBED6/STAT1/AIM2 axis through mClinical and translational medicine · 2026Article
- The correlation between latent types of emotional processing, physical exercise and aggressive behavior among middle school students: a study based on latent profile analysis.Frontiers in psychology · 2026Article
- The USP1-WDR48 deubiquitinase complex functions as a molecular switch regulating tumor-associated macrophage activation and anti-tumor response.Cell death and differentiation · 2026Article
- Novel LncRNA Gm44763 Regulates Morphine-Induced Reward Memory via MiR-298-5p-Mediated eIF4E Translation Control.Research (Washington, D.C.) · 2026Article
- Macrophages lacking TSC2 have mTORC1-dependent increased GPNMB and ameliorate ventricular dysfunction/remodeling after ischemia-reperfusion.Scientific reports · 2025Article
- Quercetin improves myocardial ischemia-reperfusion injury by regulating macrophage M2 polarization through Bcl-2/Beclin-1 complex.European journal of medical research · 2025Article
- Translational Control in Cardiac Pathophysiology and Therapeutic Development: When mRNA Meets the Heart.International journal of molecular sciences · 2025Review
- Unravelling heart failure cellular signalling heterogeneity with spatial transcriptomics.European heart journal · 2025Article
- Dysfunctional cardiomyocyte signalling and heart disease.Current opinion in cell biology · 2025Review
- Biological function of RNA-binding proteins in myocardial infarction: a potential emerging therapeutic limelight.Cell & bioscience · 2025Review
- Regulatory roles of PIWI-interacting RNAs in cardiovascular disease.American journal of physiology. Heart and circulatory physiology · 2025Review
- The cyclic metabolic switching theory of intermittent fasting.Nature metabolism · 2025Review
Corrections and comments
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Authors and funding
25 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe myocardium adapts to ischemia/reperfusion (I/R) by changes in gene expression, determining the cardiac response to reperfusion. mRNA translation is a key component of gene expression. It is largely unknown how regulation of mRNA translation contributes to cardiac gene expression and inflammation in response to reperfusion and whether it can be targeted to mitigate I/R injury.
methodsTo examine translation and its impact on gene expression in response to I/R, we measured protein synthesis after reperfusion in vitro and in vivo. Underlying mechanisms of translational control were examined by pharmacological and genetic targeting of translation initiation in mice. Cell type-specific ribosome profiling was performed in mice that had been subjected to I/R to determine the impact of mRNA translation on the regulation of gene expression in cardiomyocytes. Translational regulation of inflammation was studied by quantification of immune cell infiltration, inflammatory gene expression, and cardiac function after short-term inhibition of translation initiation.
resultsReperfusion induced a rapid recovery of translational activity that exceeds baseline levels in the infarct and border zone and is mediated by translation initiation through the mTORC1 (mechanistic target of rapamycin complex 1)-4EBP1 (eIF4E-binding protein 1)-eIF (eukaryotic initiation factor) 4F axis. Cardiomyocyte-specific ribosome profiling identified that I/R increased translation of mRNA networks associated with cardiac inflammation and cell infiltration. Short-term inhibition of the mTORC1-4EBP1-eIF4F axis decreased the expression of proinflammatory cytokines such as Ccl2 (C-C motif chemokine ligand 2) of border zone cardiomyocytes, thereby attenuating Ly6C
conclusionsGlobal protein synthesis is inhibited during ischemia and shortly after reperfusion, followed by a recovery of protein synthesis that exceeds baseline levels in the border and infarct zones. Activation of mRNA translation after reperfusion is driven by mTORC1/eIF4F-mediated regulation of initiation and mediates an mRNA network that controls inflammation and monocyte infiltration to the myocardium. Transient inhibition of the mTORC1-/eIF4F axis inhibits translation and attenuates Ly6C
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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 Socratic graph.