ArticleThe American journal of pathology2017
Retrograde Lymph Flow Leads to Chylothorax in Transgenic Mice with Lymphatic Malformations.
Article in The American journal of pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Dysfunctional adipose tissue-lymphatic crosstalk in obesity.Nature reviews. Endocrinology · 2026Review
- Lymphatic Malformations With Activating KRAS Mutations Impair Lymphatic Valve Development Through Matrix Metalloproteinases.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Clinical and CT imaging features of different types of thoracic complex lymphatic anomaly.Quantitative imaging in medicine and surgery · 2025Article
- Central conducting lymphatic anomaly: from bench to bedside.The Journal of clinical investigation · 2024Review
- Lymphatic Vascular Permeability.Cold Spring Harbor perspectives in medicine · 2022Review
- Impact of High Fat Diet and Bolus Feeding on Chyle Accumulation in a Mouse Model of Generalized Lymphatic Anomaly.Lymphatic research and biology · 2022Article
- Article
- Review
- Lymphatic Endothelial Cell Junctions: Molecular Regulation in Physiology and Diseases.Frontiers in physiology · 2020Review
- Characterizing Lymphangiogenesis and Concurrent Inflammation in Adipose Tissue in Response to VEGF-D.Frontiers in physiology · 2020Article
- Generalized Lymphatic Anomaly and Gorham-Stout Disease: Overview and Recent Insights.Advances in wound care · 2019Review
- 3-Methylcholanthrene Induces Chylous Ascites in TCDD-Inducible Poly-ADP-Ribose Polymerase (International journal of molecular sciences · 2019Article
- Vascular Endothelial Growth Factor-D (VEGF-D) Overexpression and Lymphatic Expansion in Murine Adipose Tissue Improves Metabolism in Obesity.The American journal of pathology · 2019Article
- Article
- Intraluminal valves: development, function and disease.Disease models & mechanisms · 2017Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Chylous pleural effusion (chylothorax) frequently accompanies lymphatic vessel malformations and other conditions with lymphatic defects. Although retrograde flow of chyle from the thoracic duct is considered a potential mechanism underlying chylothorax in patients and mouse models, the path chyle takes to reach the thoracic cavity is unclear. Herein, we use a novel transgenic mouse model, where doxycycline-induced overexpression of vascular endothelial growth factor (VEGF)-C was driven by the adipocyte-specific promoter adiponectin (ADN), to determine how chylothorax forms. Surprisingly, 100% of adult ADN-VEGF-C mice developed chylothorax within 7 days. Rapid, consistent appearance of chylothorax enabled us to examine the step-by-step development in otherwise normal adult mice. Dynamic imaging with a fluorescent tracer revealed that lymph in the thoracic duct of these mice could enter the thoracic cavity by retrograde flow into enlarged paravertebral lymphatics and subpleural lymphatic plexuses that had incompetent lymphatic valves. Pleural mesothelium overlying the lymphatic plexuses underwent exfoliation that increased during doxycycline exposure. Together, the findings indicate that chylothorax in ADN-VEGF-C mice results from retrograde flow of chyle from the thoracic duct into lymphatic tributaries with defective valves. Chyle extravasates from these plexuses and enters the thoracic cavity through exfoliated regions of the pleural mesothelium.
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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.