Title:Generation of a Chimeric Plasmin-resistant VEGF165/VEGF183 (132-158) Protein and its Comparative Activity
Volume: 20
Issue: 8
Author(s): Zhang Huiyong, Lu Yong, Sun Yunxiao, Zhu Wuling, Liu Jingjing and Li Taiming
Affiliation:
Keywords:
Angiogenesis, matrix metalloproteinases, plasmin, Pichia pastoris, tissue engineering, vascular endothelial growth
factor.
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.
