This review surveys a range of approaches using plasmid DNA encoding the 16
5-amino-acid isoform of vascular endothelial growth factor (phVEGF(165)) to
therapeutically modulate micro- or macrovascular endothelial cells, focusi
ng on strategies to augment postnatal collateral circulation in arterial in
sufficiency or to accelerate re-endothelialization after balloon angioplast
y to prevent restenosis. We focus on intra-arterial and intramuscular/intra
myocardial gene transfer of the VEGF(165) gene, the options that have been
most thoroughly studied to date in patients. We review developmental and po
stnatal significance of the endothelial-cell-specific mitogen VEGF that has
stimulated these studies and present limitations of current knowledge as w
ell as challenges for the future.