Background： Hereditary hemorrhagic telangiectasia （HHT） is mucocutaneous tclangiectasia, and arteriovenous malformations an autosomal dominant disease characterized by recurrent epistaxis. The efficacy of tradition...Background： Hereditary hemorrhagic telangiectasia （HHT） is mucocutaneous tclangiectasia, and arteriovenous malformations an autosomal dominant disease characterized by recurrent epistaxis. 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 ahnost 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.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China （No. 81200368） and Project involving ＂Famous Clinical Doctor in Xiang-Ya Medical College, Central South University＂ （2012-2014） and General project of science and technology of Hunan science and Technology Department 2011 WK3043.
文摘Background： Hereditary hemorrhagic telangiectasia （HHT） is mucocutaneous tclangiectasia, and arteriovenous malformations an autosomal dominant disease characterized by recurrent epistaxis. 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 ahnost 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.
