Conditional switching of VEGF provides new insights into adult neovascularization and pro-angiogenic therapy

摘要: To gain insight into neovascularization of adult organs and to uncover inherent obstacles in vascular endothelial growth factor (VEGF)-based therapeutic angiogenesis, a transgenic system for conditional switching VEGF expression was devised. The allows reversible induction specifically the heart muscle or liver at any selected schedule, thereby circumventing embryonic lethality due developmental misexpression VEGF. Using this system, we demonstrate progressive, unlimited ramification existing vasculature. In absence spatial cues, however, abnormal trees were produced, consequence chaotic connections with network formation irregularly shaped sac-like vessels. also caused massive highly disruptive edema. Importantly, premature cessation stimulus led regression most acquired vessels, thus challenging utility approaches relying on short duration. A critical transition point defined beyond which remodeled new vessels persisted months after withdrawing VEGF, conferring long-term improvement organ perfusion. This novel genetic highlights remaining problems implementation pro-angiogenic therapy.