VEGF GENE DELIVERY TO MUSCLE - POTENTIAL ROLE FOR VASCULOGENESIS IN ADULTS

Constitutive expression of VEGF after implantation of genetically engi neered myoblasts into non-ischemic muscle led to an increase in vascul ar structures. Previously, effects of VEGF delivery to adult muscle ha ve only been reported in ischemic tissues. The resulting vascular stru ctures were reminiscent of those formed during embryonic vasculogenesi s, rather than angiogenesis, sprouting from preexisting vessels. Initi ally, VEGF caused an accumulation of endothelial cells and macrophages , followed by networks of vascular channels and hemangiomas with local ly high serum VEGF levels. No effects were evident in adjacent tissue or contralateral legs, where low serum VEGF was detected. These data s uggest that the induction by VEGF of angiogenesis or vasculogenesis ma y be dose-dependent. Furthermore, VEGF expression must be carefully mo dulated, as overexpression is deleterious.