ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2021
Sonic hedgehog is expressed in human brain arteriovenous malformations and induces arteriovenous malformations in vivo.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 3 of them syntheses that pooled it.
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Who cites it
12 citing papers in PubMed, 3 syntheses or guidelines 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
- Capillary malformation-arteriovenous malformation syndrome (CM-AVM): a systematic review of cerebrovascular manifestations.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025Pooled it
- Cerebrovascular malformations different from AVMs in patients with hereditary hemorrhagic telangiectasia: a systematic review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Pooled it
- Decoding brain arteriovenous malformations: from genetic insights to modeling the vascular maze.Acta neuropathologica communications · 2026Review
- Characterizing the Microenvironment of Cerebral Arteriovenous Malformations to Test Novel Treatment Modalities.Brain sciences · 2025Review
- Changes in vascular identity during vascular remodeling.JVS-vascular science · 2025Article
- Methylome analysis of endothelial cells suggests new insights on sporadic brain arteriovenous malformation.Heliyon · 2024Article
- Cellular loci involved in the development of brain arteriovenous malformations.Frontiers in human neuroscience · 2022Review
- Therapeutic Effects of Resveratrol on Ischemia-Reperfusion Injury in the Nervous System.Neurochemical research · 2021Review
- Arteriovenous malformations: the newest Sonic hedgehog game in the postnatal brain.Neural regeneration research · 2021Article
- Dilation of Brain Veins and Perivascular Infiltration by Glioblastoma Cells in anBioMed research international · 2021Article
- Evidence for endothelial-to-mesenchymal transition in human brain arteriovenous malformations.Clinical and translational medicine · 2020Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormalities in arterial versus venous endothelial cell identity and dysregulation of angiogenesis are deemed important in the pathophysiology of brain arteriovenous malformations (AVMs). The Sonic hedgehog (Shh) pathway is crucial for both angiogenesis and arterial versus venous differentiation of endothelial cells, through its dual role on the vascular endothelial growth factor/Notch signaling and the nuclear orphan receptor COUP-TFII. In this study, we show that Shh, Gli1 (the main transcription factor of the Shh pathway), and COUP-TFII (a target of the non-canonical Shh pathway) are aberrantly expressed in human brain AVMs. We also show that implantation of pellets containing Shh in the cornea of Efnb2/LacZ mice induces growth of distinct arteries and veins, interconnected by complex sets of arteriovenous shunts, without an interposed capillary bed, as seen in AVMs. We also demonstrate that injection in the rat brain of a plasmid containing the human Shh gene induces the growth of tangles of tortuous and dilated vessels, in part positive and in part negative for the arterial marker αSMA, with direct connections between αSMA-positive and -negative vessels. In summary, we show that the Shh pathway is active in human brain AVMs and that Shh-induced angiogenesis has characteristics reminiscent of those seen in AVMs in humans.
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