ArticleJCI insight2021
Mutations in EPHB4 cause human venous valve aplasia.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Exploring EPHB4 in gait disorders: VUS detection and phenotypic characterization in a toe-walking cohort.Global medical genetics · 2026Article
- Venous Tone is a Critical Determinant of Venous Valve Closure in the Mouse.Function (Oxford, England) · 2025Article
- Advances in the diagnosis and treatment of primary deep venous valve insufficiency.European journal of medical research · 2025Review
- Changes in vascular identity during vascular remodeling.JVS-vascular science · 2025Article
- Novel postzygoticClinical case reports · 2024Article
- Recent advances of the Ephrin and Eph family in cardiovascular development and pathologies.iScience · 2024Review
- Eph-ephrin signaling couples endothelial cell sorting and arterial specification.Nature communications · 2024Article
- New targets of nascent lymphatic vessels in ocular diseases.Frontiers in physiology · 2024Review
- Targeted therapies for vascular malformations.Frontiers in medicine · 2024Review
- Endovenous thermal ablation of superficial truncal veins and compression therapy result in symptom relief in venous valve aplasia.Journal of vascular surgery cases and innovative techniques · 2023Article
- EPHB4-RASA1-Mediated Negative Regulation of Ras-MAPK Signaling in the Vasculature: Implications for the Treatment of EPHB4- and RASA1-Related Vascular Anomalies in Humans.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Osteopathy in Complex Lymphatic Anomalies.International journal of molecular sciences · 2022Review
- Angiogenesis depends upon EPHB4-mediated export of collagen IV from vascular endothelial cells.JCI insight · 2022Article
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 3 countries.
Funding
Abstract
Venous valve (VV) failure causes chronic venous insufficiency, but the molecular regulation of valve development is poorly understood. A primary lymphatic anomaly, caused by mutations in the receptor tyrosine kinase EPHB4, was recently described, with these patients also presenting with venous insufficiency. Whether the venous anomalies are the result of an effect on VVs is not known. VV formation requires complex "organization" of valve-forming endothelial cells, including their reorientation perpendicular to the direction of blood flow. Using quantitative ultrasound, we identified substantial VV aplasia and deep venous reflux in patients with mutations in EPHB4. We used a GFP reporter in mice to study expression of its ligand, ephrinB2, and analyzed developmental phenotypes after conditional deletion of floxed Ephb4 and Efnb2 alleles. EphB4 and ephrinB2 expression patterns were dynamically regulated around organizing valve-forming cells. Efnb2 deletion disrupted the normal endothelial expression patterns of the gap junction proteins connexin37 and connexin43 (both required for normal valve development) around reorientating valve-forming cells and produced deficient valve-forming cell elongation, reorientation, polarity, and proliferation. Ephb4 was also required for valve-forming cell organization and subsequent growth of the valve leaflets. These results uncover a potentially novel cause of primary human VV aplasia.
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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.