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Arterial endoglin does not protect against arteriovenous malformations

Lookup NU author(s): Dr Esha Singh, Dr Rachael Redgrave, Dr Helen PhillipsORCiD, Professor Helen ArthurORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Introduction Endoglin (ENG) forms a receptor complex with ALK1 in endothelial cells (ECs) to promote BMP9/10 signalling. Loss of function mutations in either ENG or ALK1 genes lead to the inherited vascular disorder hereditary haemorrhagic telangiectasia (HHT), characterised by arteriovenous malformations (AVMs). However, the vessel-specifc role of ENG and ALK1 proteins in protecting against AVMs is unclear. For example, AVMs have been described to initiate in arterioles, whereas ENG is predominantly expressed in venous ECs. To investigate whether ENG has any arterial involvement in protecting against AVM formation, we specifcally depleted the Eng gene in venous and capillary endothelium whilst maintaining arterial expression, and investigated how this afected the incidence and location of AVMs in comparison with pan-endothelial Eng knockdown. Methods Using the mouse neonatal retinal model of angiogenesis, we frst established the earliest time point at which ApjCre-ERT2 activity was present in venous and capillary ECs but absent from arterial ECs. We then compared the incidence of AVMs following pan-endothelial or venous/capillary-specifc ENG knockout. Results Activation of Apj-Cre-ERT2 with tamoxifen from postnatal day (P) 5 ensured preservation of arterial ENG protein expression. Specifc loss of ENG expression in ECs of veins and capillaries led to retinal AVMs at a similar frequency to pan-endothelial loss of ENG. AVMs occurred in the proximal as well as the distal part of the retina consistent with a defect in vascular remodelling during maturation of the vasculature. Conclusion Expression of ENG is not required in arterial ECs to protect against AVM formation

Publication metadata

Author(s): Singh E, Redgrave RE, Phillips HM, Arthur HA

Publication type: Article

Publication status: Published

Journal: Angiogenesis

Year: 2020

Volume: 23

Pages: 559-566

Print publication date: 01/11/2020

Online publication date: 06/06/2020

Acceptance date: 26/05/2020

Date deposited: 25/06/2020

ISSN (print): 0969-6970

ISSN (electronic): 1573-7209

Publisher: Springer


DOI: 10.1007/s10456-020-09731-z


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Funder referenceFunder name
PG/18/25/33587British Heart Foundation
PG/18/32/33760British Heart Foundation
the Cookson Trust
RG/12/2/29416British Heart Foundation