VASCULAR GENE-TRANSFER FOR THE TREATMENT OF RESTENOSIS AND ATHEROSCLEROSIS

Local gene transfer into the vascular wall offers a promising alternat ive to treat atherosclerosis-related diseases at cellular and molecula r levels. Blood vessels are among the easiest targets for gene therapy because of novel percutaneous, catheter-based treatment methods. On t he other hand, gene transfer to the artery wall can also be accomplish ed from adventitia, and in some situations intramuscular gene delivery is also a possibility. In most conditions, such as postangioplasty re stenosis, only a temporary expression of the transfected gene will be required. Promising therapeutic effects have been obtained in animal m odels of restenosis with the transfer of genes for vascular endothelia l growth factor, fibroblast growth factor, thymidine kinase, p53, bcl- x, nitric oxide synthase and retinoblastoma. Also, growth arrest homeo box 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 i schemic diseases. In addition, hyperlipoproteinemias may be improved b y 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 studie s regarding gene delivery methods, vectors and safety of the procedure s are needed before a full therapeutic potential of gene therapy in va scular diseases can be evaluated. Curr Opin Lipidol 9:465-469. (C) 199 8 Lippincott Williams & Wilkins