ten Dijke Peter, Goumans Marie-José, Pardali Evangelia
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.
Angiogenesis. 2008;11(1):79-89. doi: 10.1007/s10456-008-9101-9. Epub 2008 Feb 19.
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.
内皮糖蛋白是转化生长因子-β（TGF-β）的跨膜辅助受体，主要在增殖的内皮细胞上表达。内皮糖蛋白缺陷的小鼠在妊娠中期因心血管缺陷而死亡。内皮糖蛋白和激活素受体样激酶1（ALK1，一种内皮特异性TGF-β I型受体）的突变与遗传性出血性毛细血管扩张症（HHT）有关，HHT是一种常染色体显性血管发育异常，其特征为毛细血管扩张和动静脉畸形。内皮糖蛋白杂合子小鼠会出现类似HHT的血管异常，肿瘤和缺血后血管生成受损，并表现出内皮型一氧化氮合酶依赖性的血管张力调节恶化。在子痫前期，已证明胎盘来源的内皮糖蛋白强烈上调，且高水平的可溶性内皮糖蛋白释放到循环中。发现可溶性内皮糖蛋白通过诱导内皮细胞功能障碍，在子痫前期的发病机制中与可溶性血管内皮生长因子受体1协同作用。内皮糖蛋白在肿瘤相关内皮中高度表达，内皮糖蛋白抗体已成功用于靶向活化的内皮细胞，并在肿瘤小鼠模型中引发抗血管生成作用。这些令人兴奋的进展为开发针对血管异常疾病的新疗法提供了机会。
