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Extracranial arteriovenous malformations: towards etiology-based therapeutic management
Julien Coulie, … , Miikka Vikkula, Laurence M. Boon
Julien Coulie, … , Miikka Vikkula, Laurence M. Boon
Published March 17, 2025
Citation Information: J Clin Invest. 2025;135(6):e172837. https://doi.org/10.1172/JCI172837.
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Review

Extracranial arteriovenous malformations: towards etiology-based therapeutic management

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Abstract

Anomalies during angiogenesis can initiate the formation of arteriovenous malformations (AVMs), characterized by aberrant connections between arteries and veins and fast lesional blood flow. These anomalies can manifest anywhere in the body, including the brain, and they typically appear at birth and evolve alongside growth of the individual. Depending on their location and size, AVMs can induce progressive deformation, chronic pain, functional impairment, and ulceration and pose life-threatening risks such as hemorrhage and organ dysfunction. The primary treatment modalities entail surgical intervention or embolization followed by surgery. However, these approaches are often challenging and seldom offer definitive resolution. In addition, inadequately performed surgery may trigger angiogenic rebound, fostering AVM recurrence. Advancements in comprehending the molecular pathways underlying AVMs have sparked interest in repurposing targeted therapies initially devised for cancer treatment. The first results are promising, giving new hope to the patients affected with these often devastating and debilitating lesions, the management of which presents major clinical challenges.

Authors

Julien Coulie, Emmanuel Seront, Miikka Vikkula, Laurence M. Boon

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Figure 4

Illustration of the main pathways involved in AVMs and their functions in vascular development and maintenance.

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Illustration of the main pathways involved in AVMs and their functions i...
Selected inhibitors of these pathways are shown in magenta boxes. Red triangles indicate hyperactivating (gain of function) somatic mutations, as seen in nonsyndromic sporadic AVMs. Yellow hexagons indicate loss-of-function mutations responsible for syndromic hereditary AVMs. SMAD, fusion of Caenorhabditis elegans Sma genes and the Drosophila Mad, Mothers against decapentaplegic; RIT1, Ras like without CAAX 1.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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