Vascular gene transfer potentially offers new treatments for cardiovascular diseases.
It can be used to overexpress therapeutically important proteins and correct genetic
defects, and to test experimentally the effects of various genes in a local vascular
compartment. Vascular endothelial growth factor (VEGF) and fibroblast growth factor
(FGF) gene transfers have improved blood flow and collateral development in ischaemic
limb and myocardium. Promising therapeutic effects have been obtained in animal models
of restenosis or vein-graft thickening with the transfer of genes coding for VEGF,
nitric-oxide synthase, thymidine kinase, retinoblastoma, growth arrest homoeobox,
tissue inhibitor of metalloproteinases, cyclin or cyclin-dependent kinase inhibitors,
fas ligand and hirudin, and antisense oligonucleotides against transcription factors
or cell-cycle regulatory proteins. First experiences of VEGF gene transfer and decoy
oligonucleotides in human beings have been reported. However, further developments
in gene-transfer vectors, gene-delivery techniques and identification of effective
treatment genes will be required before the full therapeutic potential of gene therapy
in cardiovascular disease can be assessed.