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Endoglin in angiogenesis and vascular diseases

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Abstract

Endoglin is a transmembrane auxillary receptor for transforming growth factor-β (TGF-β) 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-β 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.

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Acknowledgments

Our studies on endoglin are supported by Dutch Cancer Society (UL-2005-3371) and EU grants Angiotargeting and Tumor-Host-Genomics.

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  1. 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

    Peter ten Dijke, Marie-José Goumans & Evangelia Pardali

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  1. Peter ten Dijke
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  2. Marie-José Goumans
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  3. Evangelia Pardali
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Correspondence to Peter ten Dijke.

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ten Dijke, P., Goumans, MJ. & Pardali, E. Endoglin in angiogenesis and vascular diseases. Angiogenesis 11, 79–89 (2008). https://doi.org/10.1007/s10456-008-9101-9

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