The Role of Hippo Signaling in Brain Arteriovenous Malformations: Molecular Insights into Post-Embolization Remodeling

TL;DR

This study explores how the Hippo signaling pathway, specifically YAP, influences brain arteriovenous malformations and how embolization affects vascular remodeling.

Contribution

The study reveals novel insights into the role of YAP and related molecules in bAVM remodeling after embolization.

Findings

YAP, CTGF, and CYR61 expression was significantly lower in bAVM tissues compared to healthy vessels.

Embolized bAVMs showed higher YAP, CTGF, CYR61, and FGFR1 expression, suggesting embolization promotes pro-angiogenic signaling.

Dysregulation of YAP and related molecules in bAVMs suggests potential therapeutic targets via the Hippo pathway.

Abstract

Brain arteriovenous malformations (bAVMs) are complex vascular lesions with significant clinical risks. The Hippo signaling pathway, particularly its downstream effector YAP, plays a crucial role in angiogenesis and vascular remodeling. This study investigates the role of YAP and related molecular markers in bAVMs, focusing on the effects of embolization. Immunohistochemical analysis was conducted on tissue samples from bAVM patients (n = 127), as well as on healthy blood vessels (n = 17). YAP, HIF-1α, FGFR1, CTGF, and CYR61 expression were quantified and correlated with clinical parameters. Results: In healthy vessels, YAP exhibited nuclear localization in (sub)endothelial cells and the tunica media, while CTGF and CYR61 were detected in the cytoplasm and extracellular matrix. The expression of YAP, CTGF, and CYR61 was significantly lower in bAVM tissues. Embolized bAVMs exhibited significantly higher expression of YAP, CTGF, and CYR61 compared to non-embolized tissues, suggesting a link between embolization and pro-angiogenic signaling. Additionally, FGFR1 was upregulated in embolized tissues. These results suggest that upregulation of YAP expression via the Hippo pathway might play a key role in bAVM pathophysiology. Embolization may further promote vascular remodeling. Dysregulation of YAP and related molecules in bAVMs warrants further studies to explore potential therapeutic strategies targeting the Hippo pathway.

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