ArticleThe Journal of experimental medicine2021
Hypoxia-inducible factors individually facilitate inflammatory myeloid metabolism and inefficient cardiac repair.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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Who cites it
49 citing papers in PubMed, 65 citations in OpenAlex.
- Roles of inflammation and metabolic dysfunction in cardiovascular diseases: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- The role of hypoxia-inducible factors in myocardial ischaemia-reperfusion injury and cardioprotection.Nature reviews. Cardiology · 2026Review
- Cadherin 1 negatively regulates SARS-CoV-2 infection in the olfactory epithelium.EMBO reports · 2026Article
- Reprogramming macrophage metabolism for cardiovascular therapy: From molecular pathways to precision nanomedicine.Materials today. Bio · 2026Review
- Dynamic regulation of the 'mitochondria‑immune axis' in myocardial infarction: Molecular mechanisms driving macrophage polarization through energy metabolism disorders (Review).Molecular medicine reports · 2026Review
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- Hypoxia-inducible factors link inflammation and lipid metabolism in atherosclerotic macrophages.Frontiers in cardiovascular medicine · 2026Review
- Itaconate modulates myeloid inflammation in myocardial infarction via metabolic and structural reprogramming.Genes & genomics · 2026Article
- The effect of acetyl tributyl citrate on coronary heart disease: a comprehensive computational analysis.BMC pharmacology & toxicology · 2025Article
- Review
- Immunometabolism in heart failure.Nature reviews. Cardiology · 2025Review
- Article
- FOSB is a key factor in the genetic link between inflammatory bowel disease and acute myocardial infarction: multiple bioinformatics analyses and validation.BMC medical genomics · 2025Article
- The role of long non-coding RNAs in cardiovascular diseases: A comprehensive review.Non-coding RNA research · 2025Review
- MICRORNA-146B TARGETS HIF-1Α AND ATTENUATES CARDIOMYOCYTE APOPTOSIS AND FIBROSIS IN DOXORUBICIN-INDUCED HEART FAILURE.Shock (Augusta, Ga.) · 2025Article
- Identification of novel ferroptosis-related biomarkers associated with the oxidative stress pathways in ischemic cardiomyopathy.International journal of cardiology. Heart & vasculature · 2025Article
- Mechanical regulation of macrophage metabolism by allograft inflammatory factor 1 leads to adverse remodeling after cardiac injury.Nature cardiovascular research · 2025Article
- Macrophage metabolism in inflammatory heart disease: new insights and therapeutic implications.Frontiers in medicine · 2025Review
- Cluster Headache and Hypoxia: Breathing New Life into an Old Theory, with Novel Implications.Neurology international · 2024Review
- Hypoxia sensing in resident cardiac macrophages regulates monocyte fate specification following ischemic heart injury.Nature cardiovascular research · 2024Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Hypoxia-inducible factors (HIFs) are activated in parenchymal cells in response to low oxygen and as such have been proposed as therapeutic targets during hypoxic insult, including myocardial infarction (MI). HIFs are also activated within macrophages, which orchestrate the tissue repair response. Although isoform-specific therapeutics are in development for cardiac ischemic injury, surprisingly, the unique role of myeloid HIFs, and particularly HIF-2α, is unknown. Using a murine model of myocardial infarction and mice with conditional genetic loss and gain of function, we uncovered unique proinflammatory roles for myeloid cell expression of HIF-1α and HIF-2α during MI. We found that HIF-2α suppressed anti-inflammatory macrophage mitochondrial metabolism, while HIF-1α promoted cleavage of cardioprotective MerTK through glycolytic reprogramming of macrophages. Unexpectedly, combinatorial loss of both myeloid HIF-1α and HIF-2α was catastrophic and led to macrophage necroptosis, impaired fibrogenesis, and cardiac rupture. These findings support a strategy for selective inhibition of macrophage HIF isoforms and promotion of anti-inflammatory mitochondrial metabolism during ischemic tissue repair.
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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.