Down-Regulation of Vascular Endothelial Growth Factor and Up-Regulation of Pigment Epithelium Derived Factor Make Low Molecular Weight Heparin-Endostatin and Polyethylene Glycol-Endostatin Potential Candidates for Anti-angiogenesis Drug

摘要

The aim was to study the effects and action mechanism of endostatin (ES), low molecular weight heparin-endostatin (LMWH-ES) and polyethylene glycol-endostatin (PEG-ES) on endothelial cell proliferation, choroidal neovascularization and zebrafish angiogenesis. Three-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide was used to study the effects of ES and its derivatives on endothelial cell proliferation in vitro. Choroidal neovascularization model was used to evaluate the effects of ES and its derivatives on choroidal neovascularization in vivo. Western blotting was employed to study the effects of ES and its derivatives on the expression of vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) in chorioid tissues. Zebratish model was also used to study the anti-angiogenesis activities of ES and its derivatives. The results showed that ES and its derivatives could significantly inhibit endothelial cell proliferation in vitro (p<0.05), suppress choroidal neovascularization by down-regulating expression of VEGF and up-regulating expression of PEDF in chorioid tissues, and restrain angiogenesis in zebrafish. ES showed better activity in inhibiting endothelial cell proliferation in vitro (p<0.05), but LMWH-ES and PEG-ES showed higher activity in inhibiting choroidal neovascularization in vivo (p<0.05) and angiogenesis in zebrafish (p<0.05). These results indicate that LMWH-endostatin and PEG-endostatin are potential candidates for anti-angiogenesis drug.