Studies of rare genetic diseases frequently reveal genes that are fundamental to life, and the familial vascular disorder HHT (hereditary haemorrhagic telangiectasia) is no exception. The majority of HHT patients are heterozygous for mutations in either the ENG (endoglin) or the ACVRL1 (activin receptor-like kinase 1) gene. Both genes are essential for angiogenesis during development and mice that are homozygous for mutations in Eng or Acvrl1 die in mid-gestation from vascular defects. Recent development of conditional mouse models in which the Eng or Acvrl1 gene can be depleted in later life have confirmed the importance of both genes in angiogenesis and in the maintenance of a normal vasculature. Endoglin protein is a co-receptor and ACVRL1 is a signalling receptor, both of which are expressed primarily in endothelial cells to regulate TGFβ (transforming growth factor β) signalling in the cardiovasculature. The role of ACVRL1 and endoglin in TGFβ signalling during angiogenesis is now becoming clearer as interactions between these receptors and additional ligands of the TGFβ superfamily, as well as synergistic relationships with other signalling pathways, are being uncovered. The present review aims to place these recent findings into the context of a better understanding of HHT and to summarize recent evidence that confirms the importance of endoglin and ACVRL1 in maintaining normal cardiovascular health.
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December 2011
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Conference Article|
November 21 2011
Angiogenesis regulation by TGFβ signalling: clues from an inherited vascular disease
Marwa Mahmoud;
Marwa Mahmoud
*Institute of Genetic Medicine, Centre for Life, Newcastle University, Newcastle upon Tyne NE1 3BZ, U.K.
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Paul D. Upton;
Paul D. Upton
†Division of Respiratory Medicine, Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, U.K.
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Helen M. Arthur
Helen M. Arthur
1
*Institute of Genetic Medicine, Centre for Life, Newcastle University, Newcastle upon Tyne NE1 3BZ, U.K.
1To whom correspondence should be addressed (email helen.arthur@ncl.ac.uk).
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Publisher: Portland Press Ltd
Received:
July 19 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem Soc Trans (2011) 39 (6): 1659–1666.
Article history
Received:
July 19 2011
Citation
Marwa Mahmoud, Paul D. Upton, Helen M. Arthur; Angiogenesis regulation by TGFβ signalling: clues from an inherited vascular disease. Biochem Soc Trans 1 December 2011; 39 (6): 1659–1666. doi: https://doi.org/10.1042/BST20110664
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