Involvement of the TGF-β superfamily signalling pathway in hereditary haemorrhagic telangiectasia

Hereditary haemorrhagic telangiectasia (HHT) is a vascular hereditary autosomic dominant disease associated with epistaxis, telangiectases, gastrointestinal haemorrhages and arteriovenous malformations in lung, liver and brain. It affects 1-2 in 10,000 people. There are at least three different genes mutated in HHT, ENG, ACVRL1 and MADH4 that encode endoglin, activin receptor-like kinase (ALK1) and Smad4 proteins, respectively. These proteins are involved in the transforming growth factor (TGF)-β superfamily signalling pathway of vascular endothelial cells. Mutations in ENG (HHT1) and ACVRL1 (HHT2) account for more than 90% of all HHT mutations. In this article, we review the underlying molecular and cellular bases and the therapeutic approaches that have been addressed in our laboratory in recent years.