c-KIT expands the tool kit for treating arteriovenous malformation.

Authors

Ruilin Wu, Jason E Fish

Published in

The Journal of clinical investigation. Volume 136. Issue 19. Oct 01, 2026. Epub Oct 01, 2026.

Abstract

Hereditary hemorrhagic telangiectasia (HHT) is characterized by fragile, enlarged vessels with arteriovenous connections, which can form arteriovenous malformations (AVMs) that are prone to rupture. It is driven by mutations in TGF‑β pathway genes that disrupt endothelial cell responses and blood vessel remodeling. Two studies published in this issue of the JCI identify c‑KIT as a central mediator of HHT vascular pathology. Gahn et al. showed that SMAD4 loss derepressed c‑KIT, whose activity in the junctional mechanosensory receptor complex of endothelial cells reset the fluid shear stress set point to drive maladaptive vascular remodeling. Drapé et al. demonstrated that ALK1 loss in a mouse model of HHT induced a regional pro‑angiogenic c‑KIT+ endothelial state in brain AVMs. Both studies showed that pharmacologic c-KIT inhibition mitigated disease, revealing an unexpected, potentially ligand‑independent role for c‑KIT and highlighting a promising therapeutic target.

PMID:
42820304
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

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