title: Generation of a chimeric plasmin-resistant VEGF165/VEGF183 (132-158) protein and its comparative activity.
abstract: Vascular endothelial growth factor-A (VEGF) is a potentially ideal angiogenic agent in tissue repair, however, various side effects still limit its application in clinical practice. If VEGF could be localized and activated in a specific region, its side effects would be minimized. A VEGF variant was designed by fusing the peptide VEGF183 (132-158), which contains plasmin and matrix metalloproteinases (MMPs ) cleavage sites, as well as extracellular matrix (ECM) binding sequences to the COOH-terminus of plasmin-resistant VEGF165 (designated as VEGF192). These were then expressed in Pichia pastoris and mouse breast cancer EMT-6 cells. Its stimulation of dermal vessel permeability in rats, mitogenic activity in cultured human umbilical vein endothelial cells (HUVECs), affinity for ECM, as well as its half-life in rats were compared with those of VEGF165. The results show that VEGF192 has weaker vessel permeabilization activity and mitogenic activity for HUVECs only at lower concentrations. It also has a longer half-life and a higher ECM-binding affinity compared with those of VEGF165. However, the plasmin-cleaved VEGF192 could stimulate HUVEC proliferation in a dose-dependent manner. Different functional peptide combinations should have potential applications for VEGF modifications and VEGF192 might be used in tissue engineering and the treatment of ischemia-related diseases.
authors.affiliation: College of life science and technology, Xinxiang Medical University, Xinxiang, P.R. China 453002.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Huiyong
authors.forename: Lu
authors.initials: L
authors.lastname: Yong
authors.forename: Sun
authors.initials: S
authors.lastname: Yunxiao
authors.forename: Zhu
authors.initials: Z
authors.lastname: Wuling
authors.forename: Liu
authors.initials: L
authors.lastname: Jingjing
authors.forename: Li
authors.initials: L
authors.lastname: Taiming
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002199:Capillary Permeability; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism*; D015870:Gene Expression; D006207:Half-Life; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010843:Pichia / Q000235:genetics; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014471:Umbilical Veins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D005341:Fibrinolysin; D020782:Matrix Metalloproteinases