title: 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.
abstract: 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. Zebrafish 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.
authors.affiliation: Institute of Biochemical and Biotechnological Drugs, School of Pharmaceutical Sciences, Shandong University, China.
authors.forename: Haining
authors.initials: H
authors.lastname: Tan
authors.forename: Guoying
authors.initials: G
authors.lastname: Mu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Liu
authors.forename: Fengshan
authors.initials: F
authors.lastname: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000188:drug therapy / Q000378:metabolism; D043169:Endostatins / Q000494:pharmacology* / Q000627:therapeutic use; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009414:Nerve Growth Factors / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D015843:Serpins / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D015027:Zebrafish; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D020533:Angiogenesis Inhibitors; D043169:Endostatins; D005136:Eye Proteins; D006495:Heparin, Low-Molecular-Weight; D009414:Nerve Growth Factors; D011092:Polyethylene Glycols; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor