ArticleAnesthesiology2020
Transcription-independent Induction of ERBB1 through Hypoxia-inducible Factor 2A Provides Cardioprotection during Ischemia and Reperfusion.
Article in Anesthesiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 33 citations in OpenAlex.
- The role of hypoxia-inducible factors in myocardial ischaemia-reperfusion injury and cardioprotection.Nature reviews. Cardiology · 2026Review
- Interplay between ischemia-reperfusion and metabolic reprogramming.Apoptosis : an international journal on programmed cell death · 2026Review
- Article
- Protective effect of Pinacidil on hypoxic-reoxygenated cardiomyocytes in vitro and in vivo via HIF-1α/HRE pathway.PloS one · 2025Article
- Article
- Hypoxia inducible factor 2α promotes tolerogenic macrophage development during cardiac transplantation through transcriptional regulation of colony stimulating factor 1 receptor.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Simultaneous proteome localization and turnover analysis reveals spatiotemporal features of protein homeostasis disruptions.Nature communications · 2024Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- The lncRNA GAS5 upregulates ANXA2 to mediate the macrophage inflammatory response during atherosclerosis development.Heliyon · 2024Article
- Simultaneous proteome localization and turnover analysis reveals spatiotemporal features of protein homeostasis disruptions.bioRxiv : the preprint server for biology · 2024Article
- Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Interplay of hypoxia-inducible factors and oxygen therapy in cardiovascular medicine.Nature reviews. Cardiology · 2023Review
- Hypoxia induces a glycolytic complex in intestinal epithelial cells independent of HIF-1-driven glycolytic gene expression.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Targeting myocardial equilibrative nucleoside transporter ENT1 provides cardioprotection by enhancing myeloid Adora2b signaling.JCI insight · 2023Article
- The Intriguing Role of Hypoxia-Inducible Factor in Myocardial Ischemia and Reperfusion: A Comprehensive Review.Journal of cardiovascular development and disease · 2023Review
- Pathological implications of cellular stress in cardiovascular diseases.The international journal of biochemistry & cell biology · 2023Review
- The Underexplored Landscape of Hypoxia-Inducible Factor 2 Alpha and Potential Roles in Tumor Macrophages: A Review.Oxygen (Basel, Switzerland) · 2023Article
- Alterations of long noncoding RNAs and mRNAs in extracellular vesicles derived from the murine heart post-ischemia-reperfusion injury.Journal of cellular and molecular medicine · 2022Article
- The Hypoxia-Adenosine Link during Myocardial Ischemia-Reperfusion Injury.Biomedicines · 2022Review
- SARS-CoV-2 Infection: Host Response, Immunity, and Therapeutic Targets.Inflammation · 2022Review
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundDuring myocardial ischemia, hypoxia-inducible factors are stabilized and provide protection from ischemia and reperfusion injury. Recent studies show that myocyte-specific hypoxia-inducible factor 2A promotes myocardial ischemia tolerance through induction of epidermal growth factor, amphiregulin. Here, the authors hypothesized that hypoxia-inducible factor 2A may enhance epidermal growth factor receptor 1 (ERBB1) expression in the myocardium that could interface between growth factors and its effect on providing tolerance to ischemia and reperfusion injury.
methodsHuman myocardial tissues were obtained from ischemic heart disease patients and normal control patients to compare ERBB1 expression. Myocyte-specific Hif2a or ErbB1 knockout mice were generated to observe the effect of Hif2a knockdown in regulating ERBB1 expression and to examine the role of ERBB1 during myocardial ischemia and reperfusion injury.
resultsInitial studies of myocardial tissues from patients with ischemic heart disease showed increased ERBB1 protein (1.12 ± 0.24 vs. 13.01 ± 2.20, P < 0.001). In contrast, ERBB1 transcript was unchanged. Studies using short hairpin RNA repression of Hif2A or Hif2a Myosin Cre+ mice directly implicated hypoxia-inducible factor 2A in ERBB1 protein induction during hypoxia or after myocardial ischemia, respectively. Repression of RNA-binding protein 4 abolished hypoxia-inducible factor 2A-dependent induction of ERBB1 protein. Moreover, ErbB1 Myosin Cre+ mice experienced larger infarct sizes (22.46 ± 4.06 vs. 46.14 ± 1.81, P < 0.001) and could not be rescued via amphiregulin treatment.
conclusionsThese findings suggest that hypoxia-inducible factor 2A promotes transcription-independent induction of ERBB1 protein and implicates epidermal growth factor signaling in protection from myocardial ischemia and reperfusion injury.
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