ArticlePhysiological genomics2018
HIF1 mediates a switch in pyruvate kinase isoforms after myocardial infarction.
Article in Physiological genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 75 citations in OpenAlex.
- Cardiac fibroblast deletion of PTBP1 modulates the profibrotic response by alternative splicing.Nature communications · 2026Article
- Article
- Obstructive Sleep Apnea and Cardiovascular Disease: Mechanisms, Diagnostics, and Emerging Therapeutic Approaches.Biomedicines · 2026Review
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- PKM2 is a key regulator of cardiac lipid metabolism in mice.Mitochondrion · 2025Article
- Review
- Macrophage plasticity and glucose metabolism: the role of immunometabolism in pulmonary arterial hypertension.Clinical science (London, England : 1979) · 2025Review
- Astragaloside IV increases PDHA1 in mesenchymal stem cell exosomes to treat myocardial infarction.Scientific reports · 2025Article
- Biological function of RNA-binding proteins in myocardial infarction: a potential emerging therapeutic limelight.Cell & bioscience · 2025Review
- Loss of PKM2 dysregulates inflammatory signaling in the infarcted murine heart.Physiological reports · 2025Article
- PTBP1 as a potential regulator of disease.Molecular and cellular biochemistry · 2024Review
- PKM2 regulates metabolic flux and oxidative stress in the murine heart.Physiological reports · 2024Article
- mMolecular neurobiology · 2024Article
- Identification of hub glycolysis-related genes in acute myocardial infarction and their correlation with immune infiltration using bioinformatics analysis.BMC cardiovascular disorders · 2024Article
- Inhibition of Pyruvate kinase M2 (PKM2) by shikonin attenuates isoproterenol-induced acute myocardial infarction via reduction in inflammation, hypoxia, apoptosis, and fibrosis.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Development and disease-specific regulation of RNA splicing in cardiovascular system.Frontiers in cell and developmental biology · 2024Review
- The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches.Basic research in cardiology · 2023Review
- METTL3-modified lncRNA-SNHG8 binds to PTBP1 to regulate ALAS2 expression to increase oxidative stress and promote myocardial infarction.Molecular and cellular biochemistry · 2023Article
- Role of Pyruvate Kinase M2 (PKM2) in Cardiovascular Diseases.Journal of cardiovascular translational research · 2023Review
- Candidate genes and their alternative splicing may be potential biomarkers of acute myocardial infarction: a study of mouse model.BMC cardiovascular disorders · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Alternative splicing of RNA is an underexplored area of transcriptional response. We expect that early changes in alternatively spliced genes may be important for responses to cardiac injury. Hypoxia inducible factor 1 (HIF1) is a key transcription factor that rapidly responds to loss of oxygen through alteration of metabolism and angiogenesis. The goal of this study was to investigate the transcriptional response after myocardial infarction (MI) and to identify novel, hypoxia-driven changes, including alternative splicing. After ligation of the left anterior descending artery in mice, we observed an abrupt loss of cardiac contractility and upregulation of hypoxic signaling. We then performed RNA sequencing on ischemic heart tissue 1 and 3 days after infarct to assess early transcriptional changes and identified 89 transcripts with altered splicing. Of particular interest was the switch in Pkm isoform expression (pyruvate kinase, muscle). The usually predominant Pkm1 isoform was less abundant in ischemic hearts, while Pkm2 and associated splicing factors (hnRNPA1, hnRNPA2B1, Ptbp1) rapidly increased. Despite increased Pkm2 expression, total pyruvate kinase activity remained reduced in ischemic myocardial tissue. We also demonstrated HIF1 binding to PKM by chromatin immunoprecipitation, indicating a direct role for HIF1 in mediating this isoform switch. Our study provides a new, detailed characterization of the early transcriptome after MI. From this analysis, we identified an HIF1-mediated alternative splicing event in the PKM gene. Pkm1 and Pkm2 play distinct roles in glycolytic metabolism and the upregulation of Pkm2 is likely to have important consequences for ATP synthesis in infarcted cardiac muscle.
Indexed as
Identifiers
What OpenQuestion holds
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.