Chimeric VEGF-ENZ7/PlGF specifically binding to VEGFR-2 accelerates skin wound healing via enhancement of neovascularization.
OBJECTIVE
VEGF-E(NZ7)/PlGF molecules composed of Orf virus-derived VEGF-E(NZ7) and human PlGF1 were previously proven to be potent angiogenic factors stimulating angiogenesis without significant enhancement of vascular leakage and inflammation in vivo. For its future clinical application, there is a pressing need to better understand the beneficial effects of VEGF-E(NZ7)/PlGF during wound healing in adulthood.


RESULTS
In this study, several angiogenic factors were administrated to skin punched wounds of both wild-type and diabetic mice. The treatment with VEGF-E(NZ7)/PlGF accelerated wound closure accompanied with enhanced angiogenesis, the process was occurring slightly faster than that in VEGF-A164 group. Moreover, the macrophage infiltration and lymphangiogenesis level in healed wounds were strikingly lower in VEGF-E(NZ7)/PlGF group than VEGF-A164 group, suggesting that the increased inflammation was the key issue preventing speedy wound healing of VEGF-A164-treated skin. Considering clinical safety, we further examined the antigenicity of chimeric VEGF-E(NZ7)/PlGF. Compared with the original VEGF-E(NZ7), the immunogenicity of VEGF-E(NZ7)/PlGF molecules was markedly decreased in mice and squirrel monkeys with the increase of PlGF1 humanized ratio.


CONCLUSIONS
These results indicate that VEGF-E(NZ7)/PlGF molecules are superior to VEGF-A for the acceleration of either normal or delayed skin wound healing and might be regarded as potential drugs in therapeutic angiogenesis.
Zheng
Yujuan
Y
Division of Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan.
Watanabe
Makoto
M
Kuraishi
Takeshi
T
Hattori
Shosaku
S
Kai
Chieko
C
Shibuya
Masabumi
M
D000818:Animals; D015153:Blotting, Western; D003920:Diabetes Mellitus / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D015514:Oncogene Proteins, Fusion / Q000494:pharmacology; D011336:Probability; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011506:Proteins / Q000494:pharmacology*; D012016:Reference Values; D012680:Sensitivity and Specificity; D012867:Skin / Q000293:injuries* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D008565:Membrane Proteins; D015514:Oncogene Proteins, Fusion; C098069:PIGF protein, human; D011506:Proteins; D042461:Vascular Endothelial Growth Factor A