ISSN 1214-0287 (on-line), ISSN 1214-021X (printed)
J Appl Biomed
Volume 8 (2010), No 3, p 169-177
DOI 10.2478/v10136-009-0020-x

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

Carmelo Bernabeu, Francisco Javier Blanco, Carmen Langa, Eva Maria Garrido-Martin, Luisa Maria Botella

Address: Carmelo Bernabeu, Centro de Investigaciones Biologicas, Ramiro de Maeztu, 9, Madrid 28040, Spain

Received 23rd February 2010.
Revised 29th April 2010.
Published online 13th May 2010.

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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)-beta 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.

transforming growth factor; endothelial cells; hereditary haemorrhagic telangiectasia; endoglin; ALK1; Smad; anti-fibrinolytic agents; estrogens

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