ArticleJCI insight2018
Von Hippel-Lindau mutations disrupt vascular patterning and maturation via Notch.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 23 citations in OpenAlex.
- Chimeric Antigen Receptor-Immune Cell-Based Therapies for Clear Cell Renal Cell Carcinoma: Latest Advancements and Directions.Cancers · 2026Review
- Endothelial von Hippel-Lindau gene deletion causes abnormal blood and lymphatic vasculature through ectopic activation of the HIF-CXCR4 axis.Development (Cambridge, England) · 2026Article
- Novel OCT Angiography Features, von Hippel-Lindau Disease Association, and Genetic Characterization of Juxtapapillary Retinal Capillary Hemangiomas.Investigative ophthalmology & visual science · 2025Article
- Predictive genomic biomarkers of therapeutic effects in renal cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Regulation of Notch1 Signalling by Long Non-Coding RNAs in Cancers and Other Health Disorders.International journal of molecular sciences · 2023Review
- A Soluble Platelet-Derived Growth Factor Receptor-β Originates via Pre-mRNA Splicing in the Healthy Brain and Is Upregulated during Hypoxia and Aging.Biomolecules · 2023Article
- Notch signalling in healthy and diseased vasculature.Open biology · 2022Review
- Review
- Clinical Pathological Features and Current Animal Models of Type 3 Macular Neovascularization.Frontiers in neuroscience · 2021Review
- Pericytes in Vascular Development.Current tissue microenvironment reports · 2020Article
- Macular Perfusion Impairment in Von Hippel-Lindau Disease Suggests a Generalized Retinal Vessel Alteration.Journal of clinical medicine · 2020Article
- Rb1/Rbl1/Vhl loss induces mouse subretinal angiomatous proliferation and hemangioblastoma.JCI insight · 2019Article
- The pericyte microenvironment during vascular development.Microcirculation (New York, N.Y. : 1994) · 2019Review
- Developmental vascular pruning in neonatal mouse retinas is programmed by the astrocytic oxygen-sensing mechanism.Development (Cambridge, England) · 2019Article
- Excess vascular endothelial growth factor-A disrupts pericyte recruitment during blood vessel formation.Angiogenesis · 2019Article
- Hypoxia, angiogenesis, and metabolism in the hereditary kidney cancers.The Journal of clinical investigation · 2019Review
- Microvascular bioengineering: a focus on pericytes.Journal of biological engineering · 2019Review
- Novel genotype-phenotype correlations in five Chinese families with Von Hippel-Lindau disease.Endocrine connections · 2018Article
- VHL and Hypoxia Signaling: Beyond HIF in Cancer.Biomedicines · 2018Review
- It Takes Two: Endothelial-Perivascular Cell Cross-Talk in Vascular Development and Disease.Frontiers in cardiovascular medicine · 2018Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Von Hippel-Lindau (VHL) gene mutations induce neural tissue hemangioblastomas, as well as highly vascularized clear cell renal cell carcinomas (ccRCCs). Pathological vessel remodeling arises from misregulation of HIFs and VEGF, among other genes. Variation in disease penetrance has long been recognized in relation to genotype. We show Vhl mutations also disrupt Notch signaling, causing mutation-specific vascular abnormalities, e.g., type 1 (null) vs. type 2B (murine G518A representing human R167Q). In conditional mutation retina vasculature, Vhl-null mutation (i.e., UBCCreER/+Vhlfl/fl) had little effect on initial vessel branching, but it severely reduced arterial and venous branching at later stages. Interestingly, this mutation accelerated arterial maturation, as observed in retina vessel morphology and aberrant α-smooth muscle actin localization, particularly in vascular pericytes. RNA sequencing analysis identified gene expression changes within several key pathways, including Notch and smooth muscle cell contractility. Notch inhibition failed to reverse later-stage branching defects but rescued the accelerated arterialization. Retinal vessels harboring the type 2B Vhl mutation (i.e., UBCCreER/+Vhlfl/2B) displayed stage-specific changes in vessel branching and an advanced progression toward an arterial phenotype. Disrupting Notch signaling in type 2B mutants increased both artery and vein branching and restored arterial maturation toward nonmutant levels. By revealing differential effects of the null and type 2B Vhl mutations on vessel branching and maturation, these data may provide insight into the variability of VHL-associated vascular changes - particularly the heterogeneity and aggressiveness in ccRCC vessel growth - and also suggest Notch pathway targets for treating VHL syndrome.
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Registered trials
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