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The role of HIF‐1, angiopoietin‐2, Dll4 and Notch1 in bleeding gastrointestinal vascular malformations and thalidomide‐associated actions: A pilot in vivo study
Author(s) -
TAN Hong Hong,
GE Zhi Zheng,
GAO Yun Jie,
CHEN Hui Min,
FANG Jing Yuan,
CHEN Hai Ying,
LIU Wen Zhong,
XIAO Shu Dong
Publication year - 2011
Publication title -
journal of digestive diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 51
eISSN - 1751-2980
pISSN - 1751-2972
DOI - 10.1111/j.1751-2980.2011.00506.x
Subject(s) - medicine , thalidomide , in vivo , angiopoietin 2 , gastrointestinal bleeding , bioinformatics , pharmacology , cancer research , gastroenterology , vegf receptors , vascular endothelial growth factor , genetics , biology , multiple myeloma
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.