ArticleScientific reports2018
Notch signaling pathway is a potential therapeutic target for extracranial vascular malformations.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Beta-Blocker Utilization in Intracranial Arteriovenous Malformations: A Narrative Review of Current Evidence, Mechanistic Rationale, and Potential Adjunctive Therapeutic Applications.Brain sciences · 2026Review
- MEK Inhibition Reduces Vascular Malformations and Gene Dysregulation in NRASPediatric blood & cancer · 2026Article
- Arteriovenous Malformations (AVMs): Molecular Pathogenesis, Clinical Features, and Emerging Therapeutic Strategies.Biomolecules · 2025Review
- Venous Malformations: Unraveling Latest Mechanisms and Bridging Gaps in Targeted Therapy Development.International journal of biological sciences · 2025Review
- Article
- Inhibition of Angiopoietin-2 rescues sporadic brain arteriovenous malformations by reducing pericyte loss.Angiogenesis · 2024Article
- Endothelial Rbpj deletion normalizes Notch4-induced brain arteriovenous malformation in mice.The Journal of experimental medicine · 2023Article
- Pericytes and vascular smooth muscle cells in central nervous system arteriovenous malformations.Frontiers in physiology · 2023Review
- A human model of arteriovenous malformation (AVM)-on-a-chip reproduces key disease hallmarks and enables drug testing in perfused human vessel networks.Biomaterials · 2022Article
- Computational analysis of the role of mechanosensitive Notch signaling in arterial adaptation to hypertension.Journal of the mechanical behavior of biomedical materials · 2022Article
- The role of mural cells in hemorrhage of brain arteriovenous malformation.Brain hemorrhages · 2021Article
- Chinese Cerebrovascular Neurosurgery Society and Chinese Interventional & Hybrid Operation Society, of Chinese Stroke Association Clinical Practice Guidelines for Management of Brain Arteriovenous Malformations in Eloquent Areas.Frontiers in neurology · 2021Review
- Pathogenesis of non-hereditary brain arteriovenous malformation and therapeutic implications.Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences · 2020Review
- Pharmacological inhibition of Notch signaling regresses pre-established abdominal aortic aneurysm.Scientific reports · 2019Article
- Overview of Crosstalk Between Multiple Factor of Transcytosis in Blood Brain Barrier.Frontiers in neuroscience · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
Abstract
Notch expression has been shown to be aberrant in brain arteriovenous malformations (AVM), and targeting Notch has been suggested as an approach to their treatment. It is unclear whether extracranial vascular malformations follow the same patterning and Notch pathway defects. In this study, we examined human extracranial venous (VM) (n = 3), lymphatic (LM) (n = 10), and AV (n = 6) malformations, as well as sporadic brain AVMs (n = 3). In addition to showing that extracranial AVMs demonstrate interrupted elastin and that AVMs and LMs demonstrate abnormal α-smooth muscle actin just as brain AVMS do, our results demonstrate that NOTCH1, 2, 3 and 4 proteins are overexpressed to varying degrees in both the endothelial and mural lining of the malformed vessels in all types of malformations. We further show that two gamma secretase inhibitors (GSIs), DAPT (GSI-IX) and RO4929097, cause dose-dependent inhibition of Notch target gene expression (Hey1) and rate of migration of monolayer cultures of lymphatic endothelial cells (hLECs) and blood endothelial cells (HUVEC). GSIs also inhibit HUVEC network formation. hLECs are more sensitive to GSIs compared to HUVEC. GSIs have been found to be safe in clinical trials in patients with Alzheimer's disease or cancer. Our results provide further rationale to support testing of Notch inhibitors in patients with extracranial vascular malformations.
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