title: Thalidomide Effects in Patients with Hereditary Hemorrhagic Telangiectasia During Therapeutic Treatment and in Fli-EGFP Transgenic Zebrafish Model.
abstract: BACKGROUND
  Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by recurrent epistaxis, mucocutaneous telangiectasia, and arteriovenous malformations. The efficacy of traditional treatments for HHT is very limited. The aim of this study was to investigate the therapeutic role of thalidomide in HHT patients and the effect in FLI-EGFP transgenic zebrafish model.
  
  
  METHODS
  HHT was diagnosed according to Shovlin criteria. Five HHT patients were treated with thalidomide (100 mg/d). The Epistaxis Severity Score (ESS), telangiectasia spots, and hepatic computed tomography angiography (CTA) were used to assess the clinical efficacy of thalidomide. The Fli-EGFP zebrafish model was investigated for the effect of thalidomide on angiogenesis. Dynamic real-time polymerase chain reaction assay, ELISA and Western blotting from patient's peripheral blood mononuclear cells and plasma were used to detect the expression of transforming growth factor beta 3 (TGF-β3) messenger RNA (mRNA) and vascular endothelial growth factor (VEGF) protein before and after 6 months of thalidomide treatment.
  
  
  RESULTS
  The average ESS before and after thalidomide were 6.966 ± 3.093 and 1.799 ± 0.627, respectively (P = 0.009). The "telangiectatic spot" on the tongue almost vanished; CTA examination of case 2 indicated a smaller proximal hepatic artery and decreased or ceased hepatic artery collateral circulation. The Fli-EGFP zebrafish model manifested discontinuous vessel development and vascular occlusion (7 of 10 fishes), and the TGF-β3 mRNA expression of five patients was lower after thalidomide therapy. The plasma VEGF protein expression was down-regulated in HHT patients.
  
  
  CONCLUSIONS
  Thalidomide reverses telangiectasia and controls nosebleeds by down-regulating the expression of TGF-β3 and VEGF in HHT patients. It also leads to vascular remodeling in the zebrafish model.
authors.forename: Hong-Ling
authors.initials: HL
authors.lastname: Peng
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Yi
authors.forename: Shun-Ke
authors.initials: SK
authors.lastname: Zhou
authors.forename: Si-Si
authors.initials: SS
authors.lastname: Xie
authors.affiliation: Division of Hematology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
authors.forename: Guang-Sen
authors.initials: GS
authors.lastname: Zhang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000188:drug therapy* / Q000378:metabolism; D013792:Thalidomide / Q000627:therapeutic use*; D053782:Transforming Growth Factor beta3 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D015027:Zebrafish
chemical_list: D053782:Transforming Growth Factor beta3; D042461:Vascular Endothelial Growth Factor A; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D013792:Thalidomide