Vascular gene transfer potentially offers new treatments for cardiovascular
diseases. It may be used to overexpress therapeutically important proteins
and correct genetic defects, and to Lest experimentally the effects of var
ious genes in a local vascular compartment. Vascular endothelial growth fac
tor (VEGF) and fibroblast growth factor (FGF) gene transfers have improved
blood flow and collateral development in ischemic limb and myocardium. Prom
ising therapeutic effects have been obtained in animal models of restenosis
or vein-graft thickening with the transfer of genes coding for VEGF, nitri
c-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 del
ivery techniques and identification of effective treatment genes will be re
quired before the full therapeutic potential of gene therapy in cardiovascu
lar disease can be assessed.