ArticleNature communications2018
Hypoxia-inducible factor 2-alpha-dependent induction of amphiregulin dampens myocardial ischemia-reperfusion injury.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 117 citations in OpenAlex.
- Circadian mechanisms in heart failure: Cell-specific regulation and chrono-medicine.Cell insight · 2026Review
- Amyloid-Forming Amylin Secreted by the Pancreas Promotes Hypoxia-Inducible Factor Activation and Mitochondrial Alterations in Liver and Heart During Type 2 Diabetes Pathogenesis.Comprehensive physiology · 2026Article
- The role of hypoxia-inducible factors in myocardial ischaemia-reperfusion injury and cardioprotection.Nature reviews. Cardiology · 2026Review
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- Targeted proteomics reveals immune protein patterns in serum from patients with calcific aortic stenosis.iScience · 2025Article
- Role of oxygen sensing and hypoxia-inducible factors in orchestrating innate immune responses.Nature immunology · 2025Review
- Astragaloside IV ameliorates cardiomyocyte injury and heart failure through hif/rho/rock pathway regulation: In vitro and in vivo insights.Journal of bioenergetics and biomembranes · 2025Article
- Amphiregulin in Fibrotic Diseases and Cancer.International journal of molecular sciences · 2025Review
- Article
- Identification and validation of hypoxia-responsive signature pathways in human cardiomyocytes.3 Biotech · 2025Article
- ARNT-dependent HIF-2α signaling protects cardiac microvascular barrier integrity and heart function post-myocardial infarction.Communications biology · 2025Article
- Protective effect of Pinacidil on hypoxic-reoxygenated cardiomyocytes in vitro and in vivo via HIF-1α/HRE pathway.PloS one · 2025Article
- Article
- Hypoxic neutrophils enflame the infarcted heart.American journal of physiology. Heart and circulatory physiology · 2024Article
- Therapeutic targeting of hypoxia inducible factor in acute respiratory distress syndrome.The Journal of physiology · 2024Review
- Ginsenoside Rg1 reduces cardiac inflammation against myocardial ischemia/reperfusion injury by inhibiting macrophage polarization.Journal of ginseng research · 2024Article
- Smart molecular probes with controllable photophysical property for smart medicine.Smart molecules : open access · 2024Review
- Adenosine A2AR in viral immune evasion and therapy: unveiling new avenues for treating COVID-19 and AIDS.Molecular biology reports · 2024Review
- Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Myocardial ischemia-reperfusion injury (IRI) leads to the stabilization of the transcription factors hypoxia-inducible factor 1-alpha (HIF1-alpha) and hypoxia-inducible factor 2-alpha (HIF2-alpha). While previous studies implicate HIF1-alpha in cardioprotection, the role of HIF2-alpha remains elusive. Here we show that HIF2-alpha induces the epithelial growth factor amphiregulin (AREG) to elicit cardioprotection in myocardial IRI. Comparing mice with inducible deletion of Hif1a or Hif2a in cardiac myocytes, we show that loss of Hif2-alpha increases infarct sizes. Microarray studies in genetic models or cultured human cardiac myocytes implicate HIF2-alpha in the myocardial induction of AREG. Likewise, AREG increases in myocardial tissues from patients with ischemic heart disease. Areg deficiency increases myocardial IRI, as does pharmacologic inhibition of Areg signaling. In contrast, treatment with recombinant Areg provides cardioprotection and reconstitutes mice with Hif2a deletion. These studies indicate that HIF2-alpha induces myocardial AREG expression in cardiac myocytes, which increases myocardial ischemia tolerance.
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Registered trials
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