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Lookup NU author(s): Professor Helen ArthurORCiD
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Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder characterized by vascular malformations. Many affected individuals develop recurrent nosebleeds, which can severely affect their quality of life and are clinically difficult to treat. We report here that treatment with thalidomide reduced the severity and frequency of nosebleeds (epistaxis) in the majority of a small group of subjects with HHT tested. The blood hemoglobin levels of the treated individuals rose as a result of reduced hemorrhage and enhanced blood vessel stabilization. In mice heterozygous for a null mutation in the Eng gene (encoding endoglin), an experimental model of HHT, thalidomide treatment stimulated mural cell coverage and thus rescued vessel wall defects. Thalidomide treatment increased platelet-derived growth factor-B (PDGF-B) expression in endothelial cells and stimulated mural cell activation. The effects of thalidomide treatment were partially reversed by pharmacological or genetic interference with PDGF signaling from endothelial cells to pericytes. Biopsies of nasal epithelium from individuals with HHT treated or not with thalidomide showed that similar mechanisms may explain the effects of thalidomide treatment in humans. Our findings demonstrate the ability of thalidomide to induce vessel maturation, which may be useful as a therapeutic strategy for the treatment of vascular malformations.
Author(s): Lebrin F, Srun S, Raymond K, Martin S, van den Brink S, Freitas C, Breant C, Mathivet T, Larrivee B, Thomas JL, Arthur HM, Westermann CJJ, Disch F, Mager JJ, Snijder RJ, Eichmann A, Mummery CL
Publication type: Article
Publication status: Published
Journal: Nature Medicine
Year: 2010
Volume: 16
Issue: 4
Pages: 420-428
Print publication date: 01/04/2010
ISSN (print): 1078-8956
ISSN (electronic): 1546-170X
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/nm.2131
DOI: 10.1038/nm.2131
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