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Lookup NU author(s): Emerita Professor Helen Arthur
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023 by the authors.Brain arteriovenous malformations (BAVMs) are a critical concern in hereditary hemorrhagic telangiectasia (HHT) patients, carrying the risk of life-threatening intracranial hemorrhage. While traditionally seen as congenital, the debate continues due to documented de novo cases. Our primary goal was to identify the precise postnatal window in which deletion of the HHT gene Endoglin (Eng) triggers BAVM development. We employed SclCreER(+);Eng2f/2f mice, enabling timed Eng gene deletion in endothelial cells via tamoxifen. Tamoxifen was given during four postnatal periods: P1–3, P8–10, P15–17, and P22–24. BAVM development was assessed at 2–3 months using latex dye perfusion. We examined the angiogenic activity by assessing vascular endothelial growth factor receptor 2 (VEGFR2) expression via Western blotting and Flk1-LacZ reporter mice. Longitudinal magnetic resonance angiography (MRA) was conducted up to 9 months. BAVMs emerged in 88% (P1–3), 86% (P8–10), and 55% (P15–17) of cases, with varying localization. Notably, the P22–24 group did not develop BAVMs but exhibited skin AVMs. VEGFR2 expression peaked in the initial 2 postnatal weeks, coinciding with BAVM onset. These findings support the “second hit” theory, highlighting the role of early postnatal angiogenesis in initiating BAVM development in HHT type I mice.
Author(s): Han C, Nguyen CL, Scherschinski L, Schriber TD, Arthur HM, Lawton MT, Oh SP
Publication type: Article
Publication status: Published
Journal: Biomedicines
Year: 2023
Volume: 11
Issue: 12
Online publication date: 27/11/2023
Acceptance date: 25/11/2023
Date deposited: 08/01/2024
ISSN (electronic): 2227-9059
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
URL: https://doi.org/10.3390/biomedicines11123153
DOI: 10.3390/biomedicines11123153
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