Endoglin-Mediated Vascular Remodeling: Mechanisms Underlying Hereditary Hemorrhagic Telangiectasia☆

Endoglin is emerging as a pivotal component of the gateway for signaling by transforming growth factor-β (TGF-β) in vascular endothelial cells. Mutations in endoglin cause a rare vascular disorder in humans known as hereditary hemorrhagic telengiectasia (HHT). Although rare, in-depth analysis of mutant mice and mononuclear cells from the blood of patients with HHT have provided novel and exciting insights into how the vasculature is formed, maintained, and repaired during disease. Here, we review recent data on how endoglin is thought to function in endothelial cells and place it in the broader context of signaling by TGF-β family members in vascular cells in general. We highlight where the controversies on underlying molecular mechanisms currently lie and indicate areas of present research focus.