ArticleThe Journal of clinical investigation2020
Decreased lymphatic HIF-2α accentuates lymphatic remodeling in lymphedema.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Interventions and platforms that direct lymphangiogenesis to restore physiological homeostasis and enhance immunoregulation.NPJ Regenerative medicine · 2026Review
- Biological Regulation of HIF-1α and Its Role in Therapeutic Angiogenesis for Treatment of Ischemic Cardiovascular Disease.International journal of molecular sciences · 2025Review
- Inhibition of Th2 Differentiation Accelerates Chronic Wound Healing by Facilitating Lymphangiogenesis.Biomedicines · 2025Article
- ARNT-dependent HIF-2α signaling protects cardiac microvascular barrier integrity and heart function post-myocardial infarction.Communications biology · 2025Article
- Advances in etiology, pathophysiology, diagnosis, and management of lymphedema: a comprehensive review.Frontiers in medicine · 2025Review
- Vascular Endothelial Growth Factor C (VEGF-C) Sensitizes Lymphatic Endothelial Cells to Oxidative-Stress-Induced Apoptosis through DNA Damage and Mitochondrial Dysfunction: Implications for Lymphedema.International journal of molecular sciences · 2024Article
- Molecular and metabolic orchestration of the lymphatic vasculature in physiology and pathology.Nature communications · 2023Review
- Abnormal Lymphatic Sphingosine-1-Phosphate Signaling Aggravates Lymphatic Dysfunction and Tissue Inflammation.Circulation · 2023Article
- Abnormal lymphatic S1P signaling aggravates lymphatic dysfunction and tissue inflammation.medRxiv : the preprint server for health sciences · 2023Article
- Endotyping COPD: hypoxia-inducible factor-2 as a molecular "switch" between the vascular and airway phenotypes?European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Editorial: Modulating lymphatic vascular growth in disease: current and potential pharmacological approaches for prevention and treatment, Volume II.Frontiers in pharmacology · 2023Article
- The lymphatic vascular system: much more than just a sewer.Cell & bioscience · 2022Review
- Hypoxia and Hypoxia-Inducible Factors in Lymphedema.Frontiers in pharmacology · 2022Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Pathologic lymphatic remodeling in lymphedema evolves during periods of tissue inflammation and hypoxia through poorly defined processes. In human and mouse lymphedema, there is a significant increase of hypoxia inducible factor 1 α (HIF-1α), but a reduction of HIF-2α protein expression in lymphatic endothelial cells (LECs). We questioned whether dysregulated expression of these transcription factors contributes to disease pathogenesis and found that LEC-specific deletion of Hif2α exacerbated lymphedema pathology. Even without lymphatic vascular injury, the loss of LEC-specific Hif2α caused anatomic pathology and a functional decline in fetal and adult mice. These findings suggest that HIF-2α is an important mediator of lymphatic health. HIF-2α promoted protective phosphorylated TIE2 (p-TIE2) signaling in LECs, a process also replicated by upregulating TIE2 signaling through adenovirus-mediated angiopoietin-1 (Angpt1) gene therapy. Our study suggests that HIF-2α normally promotes healthy lymphatic homeostasis and raises the exciting possibility that restoring HIF-2α pathways in lymphedema could mitigate long-term pathology and disability.
Indexed as
Identifiers
What OpenQuestion holds
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.