Peripheral vascular disease: preclinical models and emerging therapeutic targeting of the vascular endothelial growth factor ligand-receptor system

Introduction:
Vascular endothelial growth factor (VEGF)-A is a sought therapeutic target for PAD treatment because of its potent role in angiogenesis. However, no therapeutic benefit was achieved in VEGF-A clinical trials, suggesting that our understanding of VEGF-A biology and ischemic angiogenic processes needs development. Furthermore, alternate splicing in VEGF-A produces pro-and anti-angiogenic VEGF-A isoforms. The only difference is a 6-amino acid switch in the C-terminus of the final 8th exon of the gene. This finding has changed our understanding of VEGF-A biology and may explain the lack of benefit in VEGF-A clinical trials. In addition, it presents n…