title: The role of HIF-1, angiopoietin-2, Dll4 and Notch1 in bleeding gastrointestinal vascular malformations and thalidomide-associated actions: a pilot in vivo study.
abstract: OBJECTIVE
  To investigate plasma levels of hypoxia inducible factor-1 (HIF-1), angiopoietin-2 (Ang-2), Delta-like ligand 4 (Dll4) and Notch1 in patients with recurrent gastrointestinal bleeding due to gastrointestinal vascular malformation (GIVM) with or without thalidomide treatment.
  
  
  METHODS
  Ten eligible patients with recurrent gastrointestinal bleeding due to GIVM, who received thalidomide 100 mg/d for 4 months, were followed up for 1 year. The effective response was the proportions of patients with yearly bleeding episodes reduced by ≥50% at 1 year after treatment. Plasma levels of HIF-1, Ang-2, Dll4 and Notch1 were measured using enzyme-linked immunosorbent assay in the GIVM thalidomide treatment group before and after treatment (10 patients), the GIVM non-thalidomide treatment group (25 patients) and the control group (18 participants).
  
  
  RESULTS
  In the GIVM thalidomide treatment group, eight patients (8/10) achieved effective response and five (5/10) displayed complete cessation of bleeding. Mean plasma levels of HIF-1, Ang-2, Dll4 and Notch1 were all higher in the GIVM thalidomide and non-thalidomide treatment groups than in the control group (all P < 0.001). However, Ang-2 decreased more significantly in the effective subgroups (P = 0.003) and no-bleeding patients (P = 0.008).
  
  
  CONCLUSIONS
  HIF-1, Ang-2, Dll4 and Notch1 might participate in the formation of GIVM. Thalidomide is an effective and safe treatment agent for GIVM and its associated bleeding. The reduction degree of Ang-2 after a 4-month treatment of thalidomide may offer values for evaluating its prognosis and efficacy.
authors.affiliation: Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University School of Medicine Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Hong Hong
authors.initials: HH
authors.lastname: Tan
authors.forename: Zhi Zheng
authors.initials: ZZ
authors.lastname: Ge
authors.forename: Yun Jie
authors.initials: YJ
authors.lastname: Gao
authors.forename: Hui Min
authors.initials: HM
authors.lastname: Chen
authors.forename: Jing Yuan
authors.initials: JY
authors.lastname: Fang
authors.forename: Hai Ying
authors.initials: HY
authors.lastname: Chen
authors.forename: Wen Zhong
authors.initials: WZ
authors.lastname: Liu
authors.forename: Shu Dong
authors.initials: SD
authors.lastname: Xiao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D042702:Angiopoietin-2 / Q000097:blood / Q000502:physiology*; D002135:Calcium-Binding Proteins; D006471:Gastrointestinal Hemorrhage; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000097:blood / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000502:physiology*; D010865:Pilot Projects; D051881:Receptor, Notch1 / Q000097:blood / Q000502:physiology*; D012008:Recurrence; D013792:Thalidomide / Q000627:therapeutic use*; D054079:Vascular Malformations / Q000150:complications* / Q000188:drug therapy
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D042702:Angiopoietin-2; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D051793:Hypoxia-Inducible Factor 1; D036341:Intercellular Signaling Peptides and Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D013792:Thalidomide