title: Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U833, Collège de France, Paris, France. franck.lebrin@college-de-france.fr
authors.forename: Franck
authors.initials: F
authors.lastname: Lebrin
authors.forename: Samly
authors.initials: S
authors.lastname: Srun
authors.forename: Karine
authors.initials: K
authors.lastname: Raymond
authors.forename: Sabrina
authors.initials: S
authors.lastname: Martin
authors.forename: Stieneke
authors.initials: S
authors.lastname: van den Brink
authors.forename: Catarina
authors.initials: C
authors.lastname: Freitas
authors.forename: Christiane
authors.initials: C
authors.lastname: Bréant
authors.forename: Thomas
authors.initials: T
authors.lastname: Mathivet
authors.forename: Bruno
authors.initials: B
authors.lastname: Larrivée
authors.forename: Jean-Léon
authors.initials: JL
authors.lastname: Thomas
authors.forename: Helen M
authors.initials: HM
authors.lastname: Arthur
authors.forename: Cornelis J J
authors.initials: CJ
authors.lastname: Westermann
authors.forename: Frans
authors.initials: F
authors.lastname: Disch
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Mager
authors.forename: Repke J
authors.initials: RJ
authors.lastname: Snijder
authors.forename: Anne
authors.initials: A
authors.lastname: Eichmann
authors.forename: Christine L
authors.initials: CL
authors.lastname: Mummery
mesh_terms: D000368:Aged; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D004844:Epistaxis / Q000188:drug therapy*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000188:drug therapy*; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D006454:Hemoglobins; D020574:Proto-Oncogene Proteins c-sis; D013792:Thalidomide