Cardiovascular gene therapy.
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.
Ylä-Herttuala
S
S
A I Virtanen Institute and Department of Medicine, University of Kuopio, Finland. Seppo.YlaHerttuala@uku.fi
Martin
J F
JF
D000818:Animals; D002318:Cardiovascular Diseases / Q000628:therapy*; D016228:Endothelial Growth Factors / Q000627:therapeutic use; D005346:Fibroblast Growth Factors / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008222:Lymphokines / Q000627:therapeutic use; D020033:Protein Isoforms / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005346:Fibroblast Growth Factors