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,liverand 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 signallingpathway of vascular endothelial cells. mutations in eng (hht1) and acvrl1 (hht2) account for more than90% of all hht mutations. in this article,we review the underlying molecular and cellular bases and thetherapeutic approaches that have been addressed in our laboratory in recent years.