Role of vascular endothelial growth factor in angiodysplasia: an interventional study with thalidomide.

Abstract

BACKGROUND AND AIM:

The pathogenesis of angiodysplasia is still not fully understood and effective therapy is not available. Thalidomide was reported to be effective in the treatment of angiodysplasia, but the mechanisms underlying its activity are, as yet, unknown. We aimed to investigate the expression of vascular endothelial growth factor (VEGF) in angiodysplasia tissues, and the role of hypoxia-inducible factor-1α (HIF-1α) and basic fibroblast growth factor (bFGF) on VEGF expression in human umbilical vein endothelial cells (HUVEC). Additionally, we aimed to study the role of thalidomide in these parameters.

METHODS:

Immunohistochemistry was performed to visualize VEGF in angiodysplasia lesions. HUVEC were incubated under hypoxic conditions or in the presence of bFGF. Effects of exposure to thalidomide were studied. Cell growth was assessed in methylthiazolyte-trazolium assays. Enzyme-linked immunosorbent assays and real-time polymerase chain reaction were performed to assess the expression of VEGF at protein and mRNA levels. Western blot was performed to detect the expression of HIF-1α under hypoxic conditions.

RESULTS:

VEGF was strongly expressed in 75% of patients with angiodysplasia lesions, as compared to expression in patients without angiodysplasia lesions. VEGF was also induced in HUVEC under hypoxic conditions (P < 0.05). bFGF was found to stimulate the proliferation of HUVEC and enhance the expression of VEGF. Thalidomide suppressed bFGF-induced proliferation significantly and decreased VEGF expression, both at the protein and mRNA levels. Thalidomide also inhibited HIF-1α in a dose-dependent manner (P < 0.05).

CONCLUSIONS:

VEGF may play an important role in the pathogenesis of angiodysplasia. Thalidomide can suppress VEGF, either induced by HIF-1α or bFGF.

• Authors: Honghong Tan, Huimin Chen, Chunhong Xu, Zhizheng Ge, Yunjie Gao, Jingyuan Fang, Wenzhong Liu, Shudong Xiao
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 27 Issue 6 Pg. 1094-101 (Jun 2012) ISSN: 1440-1746 [Electronic] Australia
• PMID: 22098296 (Publication Type: Journal Article)
• Copyright: © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Chemical References

• Angiogenesis Inhibitors
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• RNA, Messenger
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Fibroblast Growth Factor 2
• Thalidomide

Topics

• Adult
• Aged
• Angiodysplasia (metabolism)
• Angiogenesis Inhibitors (pharmacology)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Female
• Fibroblast Growth Factor 2 (antagonists & inhibitors, pharmacology)
• Gene Expression Regulation (drug effects)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors, metabolism)
• Male
• Middle Aged
• RNA, Messenger (genetics)
• Thalidomide (pharmacology)
• Vascular Endothelial Growth Factor A (genetics, metabolism, physiology)
• Young Adult