Somatic gene therapy in the cardiovascular system.

This review surveys a range of approaches using plasmid DNA encoding the 165-amino-acid isoform of vascular endothelial growth factor (phVEGF165) to therapeutically modulate micro- or macrovascular endothelial cells, focusing on strategies to augment postnatal collateral circulation in arterial insufficiency or to accelerate re-endothelialization after balloon angioplasty to prevent restenosis. We focus on intra-arterial and intramuscular/intramyocardial gene transfer of the VEGF165 gene, the options that have been most thoroughly studied to date in patients. We review developmental and postnatal significance of the endothelial-cell-specific mitogen VEGF that has stimulated these studies and present limitations of current knowledge as well as challenges for the future.