ArticleCell discovery2024
The E3 ubiquitin ligase MARCH2 protects against myocardial ischemia-reperfusion injury through inhibiting pyroptosis via negative regulation of PGAM5/MAVS/NLRP3 axis.
Article in Cell discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
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Who cites it
67 citing papers in PubMed, 79 citations in OpenAlex.
- Sphingosine-1-Phosphate Attenuates LPS-Induced Inflammatory Cardiac Injury in Association With RASGRP1-S100A9-NLRP3 Signaling.Drug development research · 2026Article
- Endothelial Cell Differentiation-Related CircRNAs Drive the Differentiation of Vascular Endothelial Cells.Biochemical genetics · 2026Article
- Roles of inflammation and metabolic dysfunction in cardiovascular diseases: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Intracellular LRG1 recruits MARCH2 to ubiquitinate and degrade endothelial VE-cadherin in septic lung injury.Acta pharmacologica Sinica · 2026Article
- Review
- Review
- Tnxb Alleviates Myocardial Ischemia-Reperfusion Injury Through Facilitating Akt-Dependent Endothelial Cell Survival and Angiogenesis in Mice.Cardiovascular toxicology · 2026Article
- Ubiquitin-Related Proteostatic Programs in Cycling Fibroblast-Lineage Remodeling After Myocardial Ischemic Injury: A Hypothesis Informed by Single-Cell and Spatial Transcriptomics.International journal of molecular sciences · 2026Review
- Advances in understanding the NLRP3 inflammasome‑mediated mechanisms and therapeutic targets in diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- Dysregulation of liquid-liquid phase separation: from molecular mechanisms to targeted therapies in cardiovascular diseases.Journal of nanobiotechnology · 2026Review
- FERPIR promotes cardiomyocyte survival and attenuates cardiac remodeling after myocardial infarction.Cell death & disease · 2026Article
- Liquid-liquid phase separation-driven regulated cell death: from molecular mechanisms to therapeutic strategies.Cell death discovery · 2026Review
- N-International journal of molecular sciences · 2026Article
- MARCH2 prevents doxorubicin-induced cardiomyopathy by stabilizing NR1H2 and promoting clearance of apoptotic cardiomyocytes.Nature communications · 2026Article
- Gut microbiota dysbiosis promotes chronic kidney disease-associated atrial fibrillation through activation of the NLRP3 inflammasome.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- ALKBH3 suppresses ischemia/reperfusion-induced PANoptosis by regulating the ZBED6/STAT1/AIM2 axis through mClinical and translational medicine · 2026Article
- Molecular mechanisms of NLRP3 inflammasome activation.Experimental & molecular medicine · 2026Review
- Advances in the mechanisms of the NLRP3 inflammasome in sepsis‑induced cardiomyopathy and targeted therapeutic studies (Review).Molecular medicine reports · 2026Review
- TRIM40 Drives Pathological Cardiac Hypertrophy and Heart Failure via Ubiquitination of PKN2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting Microglial CD49a Inhibits Neuroinflammation and Demonstrates Therapeutic Potential for Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Inflammasome activation and pyroptotic cell death are known to contribute to the pathogenesis of cardiovascular diseases, such as myocardial ischemia-reperfusion (I/R) injury, although the underlying regulatory mechanisms remain poorly understood. Here we report that expression levels of the E3 ubiquitin ligase membrane-associated RING finger protein 2 (MARCH2) were elevated in ischemic human hearts or mouse hearts upon I/R injury. Genetic ablation of MARCH2 aggravated myocardial infarction and cardiac dysfunction upon myocardial I/R injury. Single-cell RNA-seq analysis suggested that loss of MARCH2 prompted activation of NLRP3 inflammasome in cardiomyocytes. Mechanistically, phosphoglycerate mutase 5 (PGAM5) was found to act as a novel regulator of MAVS-NLRP3 signaling by forming liquid-liquid phase separation condensates with MAVS and fostering the recruitment of NLRP3. MARCH2 directly interacts with PGAM5 to promote its K48-linked polyubiquitination and proteasomal degradation, resulting in reduced PGAM5-MAVS co-condensation, and consequently inhibition of NLRP3 inflammasome activation and cardiomyocyte pyroptosis. AAV-based re-introduction of MARCH2 significantly ameliorated I/R-induced mouse heart dysfunction. Altogether, our findings reveal a novel mechanism where MARCH2-mediated ubiquitination negatively regulates the PGAM5/MAVS/NLRP3 axis to protect against cardiomyocyte pyroptosis and myocardial 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.