title: Endoglin in angiogenesis and vascular diseases.
abstract: Endoglin is a transmembrane auxillary receptor for transforming growth factor-beta (TGF-beta) that is predominantly expressed on proliferating endothelial cells. Endoglin deficient mice die during midgestation due to cardiovascular defects. Mutations in endoglin and activin receptor-like kinase 1 (ALK1), an endothelial specific TGF-beta type I receptor, have been linked to hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant vascular dysplasia characterized by telangiectases and arteriovenous malformations. Endoglin heterozygote mice develop HHT-like vascular abnormalities, have impaired tumor and post-ischemic angiogenesis and demonstrate an endothelial nitric oxide synthase-dependent deterioration in the regulation of vascular tone. In pre-eclampsia, placenta-derived endoglin has been shown to be strongly upregulated and high levels of soluble endoglin are released into the circulation. Soluble endoglin was found to cooperate with a soluble form of vascular endothelial growth factor receptor 1 in the pathogenesis of pre-eclampsia by inducing endothelial cell dysfunction. Endoglin is highly expressed in tumor-associated endothelium, and endoglin antibodies have been successfully used to target activated endothelial cells and elicit anti-angiogenic effects in tumor mouse models. These exciting advances provide opportunities for the development of new therapies for diseases with vascular abnormalities.
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Building 2, Room R-02-022, Postzone S-1-P, Postbus 9600, 2300 RC, Leiden, The Netherlands. p.ten_dijke@lumc.nl
authors.forename: Peter
authors.initials: P
authors.lastname: ten Dijke
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Goumans
authors.forename: Evangelia
authors.initials: E
authors.lastname: Pardali
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D000071063:Endoglin; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D014652:Vascular Diseases / Q000378:metabolism* / Q000473:pathology
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface