Disruption of endothelial stability directly impacts vascular neighboring cells in Hereditary Hemorrhagic Telangiectasia

BACKGROUNDHereditary hemorrhagic telangiectasia (HHT) is a genetic disorder caused by pathogenic variants in the endothelial TGF{beta}/BMP pathway, crucial for the vascular arterial-venous differentiation. Vascular defects result in fragile and malformed vessels. The precise mechanisms driving vascular network failure remain incompletely understood, complicating the design of targeted therapies. METHODSNasal telangiectasias from HHT patients carrying variants in ACVRL1 or ENG were used to perform scRNA-seq (2 ACVRL1- and 1 ENG-patient) and spatial transcriptomics (1 ACVRL1 and 1 ENG) to uncover endothelial cells (EC) populations. Vascular characteristics within biopsies were evaluated using