Defective Angiogenesis in Mice Lacking Endoglin

TLDR

Endoglin is a TGF‑beta binding protein on endothelial cells, and loss‑of‑function mutations in its gene cause hereditary hemorrhagic telangiectasia, a disease marked by vascular malformations. Endoglin‑deficient mice die by gestational day 11.5 from defective vascular development, with impaired smooth‑muscle formation and endothelial remodeling, demonstrating endoglin’s essential role in angiogenesis and implicating it in HHT1 pathogenesis.

Abstract

Endoglin is a transforming growth factor-beta (TGF-beta) binding protein expressed on the surface of endothelial cells. Loss-of-function mutations in the human endoglin gene ENG cause hereditary hemorrhagic telangiectasia (HHT1), a disease characterized by vascular malformations. Here it is shown that by gestational day 11.5, mice lacking endoglin die from defective vascular development. However, in contrast to mice lacking TGF-beta, vasculogenesis was unaffected. Loss of endoglin caused poor vascular smooth muscle development and arrested endothelial remodeling. These results demonstrate that endoglin is essential for angiogenesis and suggest a pathogenic mechanism for HHT1.