These combined data suggest that bi-allelic loss of ENG or ACVRL1 may be a required event in the development of telangiectasia, and that rather than haploinsufficiency, VMs in HHT are caused by a Knudsonian two-hit mechanism.
Development of vascular malformations in HHT patients is originated mainly by mutations in ACVRL1/ALK1 (activin receptor-like kinase type I) or Endoglin (ENG) genes.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominantly inherited vascular-malformation syndrome associated with gene mutations including ENG, ACVRL1 and SMAD4 gene.
Mutations in the human gene cause hereditary hemorrhagic telangiectasia type 1 (HHT1), a disease characterized by vascular malformations that increase with age.
To better understand the role of endoglin in vascular malformation development, we examined the effect of vascular endothelial growth factor (VEGF) hyperstimulation on microvessels in adult endoglin heterozygous (Eng+/-) mice using an adenoviral vector to deliver recombinant human VEGF165 cDNA (AdhVEGF) into basal ganglia.