ArticleCirculation research2014
Pulmonary lymphangiectasia resulting from vascular endothelial growth factor-C overexpression during a critical period.
Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 69 citations in OpenAlex.
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- Three-dimensional visualization of the lymphatic, vascular and neural network in rat lung by confocal microscopy.Journal of molecular histology · 2023Article
- Small intestinal mucosal abnormalities using video capsule endoscopy in intestinal lymphangiectasia.Orphanet journal of rare diseases · 2023Article
- Hyperoxia Disrupts Lung Lymphatic Homeostasis in Neonatal Mice.Antioxidants (Basel, Switzerland) · 2023Article
- A census of the lung: CellCards from LungMAP.Developmental cell · 2022Article
- Imaging Blood Vessels and Lymphatics in Mouse Trachea Wholemounts.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Lymphatic Vessel Regression and Its Therapeutic Applications: Learning From Principles of Blood Vessel Regression.Frontiers in physiology · 2022Review
- Plastic Bronchitis-A Serious Rare Complication Affecting Children Only after Fontan Procedure?Journal of clinical medicine · 2021Article
- Lymphatic-specific intracellular modulation of receptor tyrosine kinase signaling improves lymphatic growth and function.Science signaling · 2021Article
- Vascular endothelial cell specification in health and disease.Angiogenesis · 2021Review
- Neuroinflammation-Driven Lymphangiogenesis in CNS Diseases.Frontiers in cellular neuroscience · 2021Review
- Lymphatic Proliferation Ameliorates Pulmonary Fibrosis after Lung Injury.The American journal of pathology · 2020Article
- CD146, from a melanoma cell adhesion molecule to a signaling receptor.Signal transduction and targeted therapy · 2020Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
rationaleLymphatic vessels in the respiratory tract normally mature into a functional network during the neonatal period, but under some pathological conditions they can grow as enlarged, dilated sacs that result in the potentially lethal condition of pulmonary lymphangiectasia.
objectiveWe sought to determine whether overexpression of the lymphangiogenic growth factor (vascular endothelial growth factor-C [VEGF-C]) can promote lymphatic growth and maturation in the respiratory tract. Unexpectedly, perinatal overexpression of VEGF-C in the respiratory epithelium led to a condition resembling human pulmonary lymphangiectasia, a life-threatening disorder of the newborn characterized by respiratory distress and the presence of widely dilated lymphatics. METHODS AND
resultsAdministration of doxycycline to Clara cell secretory protein-reverse tetracycline-controlled transactivator/tetracycline operator-VEGF-C double-transgenic mice during a critical period from embryonic day 15.5 to postnatal day 14 was accompanied by respiratory distress, chylothorax, pulmonary lymphangiectasia, and high mortality. Enlarged sac-like lymphatics were abundant near major airways, pulmonary vessels, and visceral pleura. Side-by-side comparison revealed morphological features similar to pulmonary lymphangiectasia in humans. The condition was milder in mice given doxycycline after age postnatal day 14 and did not develop after postnatal day 35. Mechanistic studies revealed that VEGF recptor (VEGFR)-3 alone drove lymphatic growth in adult mice, but both VEGFR-2 and VEGFR-3 were required for the development of lymphangiectasia in neonates. VEGFR-2/VEGFR-3 heterodimers were more abundant in the dilated lymphatics, consistent with the involvement of both receptors. Despite the dependence of lymphangiectasia on VEGFR-2 and VEGFR-3, the condition was not reversed by blocking both receptors together or by withdrawing VEGF-C.
conclusionsThe findings indicate that VEGF-C overexpression can induce pulmonary lymphangiectasia during a critical period in perinatal development.
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