ArticleCirculation2019
Endothelial Hypoxia-Inducible Factor-2α Is Required for the Maintenance of Airway Microvasculature.
Article in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Metabolic Adaptations and Therapies in Cardiac Hypoxia: Mechanisms and Clinical Implications/ Potential Strategies.JACC. Basic to translational science · 2025Review
- Decoding infantile hemangioma: cellular dynamics, molecular signals, and microenvironmental influences.Frontiers in oncology · 2025Review
- Sestrin2 serves as a scaffold protein to maintain cardiac energy and metabolic homeostasis during pathological stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- EPAS1 Attenuates Atherosclerosis Initiation at Disturbed Flow Sites Through Endothelial Fatty Acid Uptake.Circulation research · 2024Article
- 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
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Regorafenib modulation of the angiopoietin/TIE2 axis in a mouse model of sepsis-induced lung injury.Journal of medicine and life · 2023Article
- Review
- The Complex Relationship between Hypoxia Signaling, Mitochondrial Dysfunction and Inflammation in Calcific Aortic Valve Disease: Insights from the Molecular Mechanisms to Therapeutic Approaches.International journal of molecular sciences · 2023Review
- The Intriguing Role of Hypoxia-Inducible Factor in Myocardial Ischemia and Reperfusion: A Comprehensive Review.Journal of cardiovascular development and disease · 2023Review
- AZU1 (HBP/CAP37) and PRKCG (PKC-gamma) may be candidate genes affecting the severity of acute mountain sickness.BMC medical genomics · 2023Article
- SGLT2 Inhibitors May Restore Endothelial Barrier Interrupted by 25-Hydroxycholesterol.Molecules (Basel, Switzerland) · 2023Article
- Hypoxia represses FOXF1 in lung endothelial cells through HIF-1α.Frontiers in physiology · 2023Article
- No benefit of HIF prolyl hydroxylase inhibition for hypertensive renal damage in renovascular hypertensive rats.Frontiers in physiology · 2023Article
- A pleiotropic hypoxia-sensitiveScience advances · 2022Article
- Effect of Hypoxia on Pulmonary Endothelial Cells from Bleomycin-Induced Pulmonary Fibrosis Model Mice.International journal of molecular sciences · 2022Article
- Review
- Hypoxia and Hypoxia-Inducible Factors in Lymphedema.Frontiers in pharmacology · 2022Review
- Imaging Blood Vessels and Lymphatics in Mouse Trachea Wholemounts.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Oxygen-sensing mechanisms in development and tissue repair.Development (Cambridge, England) · 2021Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundHypoxia-inducible factors (HIFs), especially HIF-1α and HIF-2α, are key mediators of the adaptive response to hypoxic stress and play essential roles in maintaining lung homeostasis. Human and animal genetics studies confirm that abnormal HIF correlates with pulmonary vascular pathology and chronic lung diseases, but it remains unclear whether endothelial cell HIF production is essential for microvascular health. The large airway has an ideal circulatory bed for evaluating histological changes and physiology in genetically modified rodents.
methodsThe tracheal microvasculature of mice, with conditionally deleted or overexpressed HIF-1α or HIF-2α, was evaluated for anatomy, perfusion, and permeability. Angiogenic signaling studies assessed vascular changes attributable to dysregulated HIF expression. An orthotopic tracheal transplantation model further evaluated the contribution of individual HIF isoforms in airway endothelial cells.
resultsThe genetic deletion of Hif-2α but not Hif-1α caused tracheal endothelial cell apoptosis, diminished pericyte coverage, reduced vascular perfusion, defective barrier function, overlying epithelial abnormalities, and subepithelial fibrotic remodeling. HIF-2α promoted microvascular integrity in airways through endothelial angiopoietin-1/TIE2 signaling and Notch activity. In functional tracheal transplants, HIF-2α deficiency in airway donors accelerated graft microvascular loss, whereas HIF-2α or angiopoietin-1 overexpression prolonged transplant microvascular perfusion. Augmented endothelial HIF-2α in transplant donors promoted airway microvascular integrity and diminished alloimmune inflammation.
conclusionsOur findings reveal that the constitutive expression of endothelial HIF-2α is required for airway microvascular health.
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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.