Vascular gene transfer for the treatment of restenosis and atherosclerosis

Local gene transfer into the vascular wall offers a promising alternative to treat atherosclerosis-related diseases at cellular and molecular levels. Blood vessels are among the easiest targets for gene therapy because of novel percutaneous, catheter-based treatment methods. On the other hand, gene transfer to the artery wall can also be accomplished from adventitia, and in some situations intramuscular gene delivery is also a possibility. In most conditions, such as postangioplasty restenosis, only a temporary expression of the transfected gene will be required. Promising therapeutic effects have been obtained in animal models of restenosis with the transfer of genes for vascular endothelial growth factor, fibroblast growth factor, thymidine kinase, p53, bcl-x, nitric oxide synthase and retinoblastoma. Also, growth arrest homeobox gene and antisense oligonucleotides against transcription factors or cell cycle regulatory proteins have produced beneficial therapeutic effects. Angiogenesis is an emerging new target for gene therapy of ischemic diseases. In addition, hyperlipoproteinemias may be improved by transferring functional lipoprotein-receptor genes into hepatocytes of affected individuals. First experiences of gene transfer methods in the human vascular system have been reported. However, further studies regarding gene delivery methods, vectors and safety of the procedures are needed before a full therapeutic potential of gene therapy in vascular diseases can be evaluated.