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Endothelial cell biology of Endoglin in hereditary hemorrhagic telangiectasia

Sugden, Wade, W.a,b,c; Siekmann, Arndt, F.a,b

Current Opinion in Hematology: May 2018 - Volume 25 - Issue 3 - p 237–244
doi: 10.1097/MOH.0000000000000419
VASCULAR BIOLOGY: Edited by Edward F. Plow

Purpose of review Mutations in the Endoglin (Eng) gene, an auxiliary receptor in the transforming growth factor beta (TGFβ)-superfamily signaling pathway, are responsible for the human vascular disorder hereditary hemorrhagic telangiectasia (HHT) type 1, characterized in part by blood vessel enlargement. A growing body of work has uncovered an autonomous role for Eng in endothelial cells. We will highlight the influence of Eng on distinct cellular behaviors, such as migration and shape control, which are ultimately important for the assignment of proper blood vessel diameters.

Recent findings How endothelial cells establish hierarchically ordered blood vessel trees is one of the outstanding questions in vascular biology. Mutations in components of the TGFβ-superfamily of signaling molecules disrupt this patterning and cause arteriovenous malformations (AVMs). Eng is a TGFβ coreceptor enhancing signaling through the type I receptor Alk1. Recent studies identified bone morphogenetic proteins (BMPs) 9 and 10 as the primary ligands for Alk1/Eng. Importantly, Eng potentiated Alk1 pathway activation downstream of hemodynamic forces. New results furthermore revealed how Eng affects endothelial cell migration and cell shape control in response to these forces, thereby providing new avenues for our understanding of AVM cause.

Summary We will discuss the interplay of Eng and hemodynamic forces, such as shear stress, in relation to Alk1 receptor activation. We will furthermore detail how this signaling pathway influences endothelial cell behaviors important for the establishment of hierarchically ordered blood vessel trees. Finally, we will provide an outlook how these insights might help in developing new therapies for the treatment of HHT.

aMax Planck Institute for Molecular Biomedicine

bCells-in-Motion Cluster of Excellence (EXC 1003 – CiM), University of Muenster, Muenster, Germany

cStem Cell Program and Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA

Correspondence to Dr Arndt F. Siekmann, Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany. Tel: +49 251 70365 459; e-mail:

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