ArticleThe Journal of clinical investigation2011
Adenovirus-mediated HIF-1α gene transfer promotes repair of mouse airway allograft microvasculature and attenuates chronic rejection.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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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.
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.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- The complex anatomy of the bronchial arteries: a meta-analysis with potential implications for thoracic surgery and hemoptysis treatment.Scientific reports · 2024Pooled it
- Hyperbaric oxygen therapy to prevent central airway stenosis after lung transplantation.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2021Trial
- New methods for monitoring dynamic airway tissue oxygenation and perfusion in experimental and clinical transplantation.American journal of physiology. Lung cellular and molecular physiology · 2012Trial
- Bronchial anastomotic complications as a microvascular disruption in a mouse model of airway transplantation.Frontiers in immunology · 2025Review
- Clinical investigation of hypoxia-inducible factors: getting there.The Journal of clinical investigation · 2024Article
- Successful tracheal regeneration using biofabricated autologous analogues without artificial supports.Scientific reports · 2022Article
- Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts.International journal of molecular sciences · 2022Article
- Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality?Frontiers in immunology · 2022Review
- Untangling Local Pro-Inflammatory, Reparative, and Regulatory Damage-Associated Molecular-Patterns (DAMPs) Pathways to Improve Transplant Outcomes.Frontiers in immunology · 2021Review
- Airway Epithelial Telomere Dysfunction Drives Remodeling Similar to Chronic Lung Allograft Dysfunction.American journal of respiratory cell and molecular biology · 2020Article
- Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants.Journal of translational medicine · 2020Article
- Deconstructing tissue engineered trachea: Assessing the role of synthetic scaffolds, segmental replacement and cell seeding on graft performance.Acta biomaterialia · 2020Article
- Apelin directs endothelial cell differentiation and vascular repair following immune-mediated injury.The Journal of clinical investigation · 2020Article
- iPSC-derived MSC therapy induces immune tolerance and supports long-term graft survival in mouse orthotopic tracheal transplants.Stem cell research & therapy · 2019Article
- Lung transplantation and beyond: continued challenges in the wake of significant progress.Journal of thoracic disease · 2019Article
- Airway hypoxia in lung transplantation.Current opinion in physiology · 2019Article
- The role of HIF-1α-VEGF pathway in bronchiolitis obliterans after lung transplantation.Journal of cardiothoracic surgery · 2019Article
- Endothelial Hypoxia-Inducible Factor-2α Is Required for the Maintenance of Airway Microvasculature.Circulation · 2019Article
- Circadian Dysregulation: The Next Frontier in Obstructive Sleep Apnea Research.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2018Review
- Acute and chronic phagocyte determinants of cardiac allograft vasculopathy.Seminars in immunopathology · 2018Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Chronic rejection, manifested as small airway fibrosis (obliterative bronchiolitis [OB]), is the main obstacle to long-term survival in lung transplantation. Recent studies demonstrate that the airways involved in a lung transplant are relatively hypoxic at baseline and that OB pathogenesis may be linked to ischemia induced by a transient loss of airway microvasculature. Here, we show that HIF-1α mediates airway microvascular repair in a model of orthotopic tracheal transplantation. Grafts with a conditional knockout of Hif1a demonstrated diminished recruitment of recipient-derived Tie2⁺ angiogenic cells to the allograft, impaired repair of damaged microvasculature, accelerated loss of microvascular perfusion, and hastened denudation of epithelial cells. In contrast, graft HIF-1α overexpression induced via an adenoviral vector prolonged airway microvascular perfusion, preserved epithelial integrity, extended the time window for the graft to be rescued from chronic rejection, and attenuated airway fibrotic remodeling. HIF-1α overexpression induced the expression of proangiogenic factors such as Sdf1, Plgf, and Vegf, and promoted the recruitment of vasoreparative Tie2⁺ cells. This study demonstrates that a therapy that enhances vascular integrity during acute rejection may promote graft health and prevent chronic rejection.
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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.