ArticleThe Journal of experimental medicine2023
Endothelial Rbpj deletion normalizes Notch4-induced brain arteriovenous malformation in mice.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Translational relevance of animal models available on brain arteriovenous malformations, a systematic review.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Pooled it
- Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026Review
- Advances in the Genetics and Molecular Biology of Brain Arteriovenous Malformations.Translational stroke research · 2026Review
- CCL17 as an Inflammatory Biomarker Enhances Cardiovascular Risk Stratification: a Prospective Cohort Study.Journal of cardiovascular translational research · 2025Article
- The Ubiquitin-Proteasome System in Asthma: Mechanisms and Therapeutic Possibilities.Clinical reviews in allergy & immunology · 2025Review
- Neuroinflammation and hypoxia promote astrocyte phenotypic transformation and propel neurovascular dysfunction in brain arteriovenous malformation.Journal of neuroinflammation · 2025Article
- From bench to bedside: murine models of inherited and sporadic brain arteriovenous malformations.Angiogenesis · 2025Review
- A non-genetic model of vascular shunts informs on the cellular mechanisms of formation and resolution of arteriovenous malformations.Cardiovascular research · 2024Article
- The Diagnostic and Prognostic Value of Neurotransmitter Receptor-Related Genes in Colon Adenocarcinoma.Molecular biotechnology · 2024Article
- Methylome analysis of endothelial cells suggests new insights on sporadic brain arteriovenous malformation.Heliyon · 2024Article
- Pericytes and vascular smooth muscle cells in central nervous system arteriovenous malformations.Frontiers in physiology · 2023Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Upregulation of Notch signaling is associated with brain arteriovenous malformation (bAVM), a disease that lacks pharmacological treatments. Tetracycline (tet)-regulatable endothelial expression of constitutively active Notch4 (Notch4*tetEC) from birth induced bAVMs in 100% of mice by P16. To test whether targeting downstream signaling, while sustaining the causal Notch4*tetEC expression, induces AVM normalization, we deleted Rbpj, a mediator of Notch signaling, in endothelium from P16, by combining tet-repressible Notch4*tetEC with tamoxifen-inducible Rbpj deletion. Established pathologies, including AV connection diameter, AV shunting, vessel tortuosity, intracerebral hemorrhage, tissue hypoxia, life expectancy, and arterial marker expression were improved, compared with Notch4*tetEC mice without Rbpj deletion. Similarly, Rbpj deletion from P21 induced advanced bAVM regression. After complete AVM normalization induced by repression of Notch4*tetEC, virtually no bAVM relapsed, despite Notch4*tetEC re-expression in adults. Thus, inhibition of endothelial Rbpj halted Notch4*tetEC bAVM progression, normalized bAVM abnormalities, and restored microcirculation, providing proof of concept for targeting a downstream mediator to treat AVM pathologies despite a sustained causal molecular lesion.
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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.