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Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Generation of a Chimeric Plasmin-resistant VEGF165/VEGF183 (132-158) Protein and its Comparative Activity

Author(s): Zhang Huiyong, Lu Yong, Sun Yunxiao, Zhu Wuling, Liu Jingjing and Li Taiming

Volume 20, Issue 8, 2013

Page: [947 - 954] Pages: 8

DOI: 10.2174/0929866511320080013

Price: $65

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.

Keywords: Angiogenesis, matrix metalloproteinases, plasmin, Pichia pastoris, tissue engineering, vascular endothelial growth factor.


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