Adenovirus-mediated arterial gene therapy for restenosis: problems and perspectives.
Restenosis remains the main limitation of interventional cardiology. Restenosis occurs when angioplasty-induced intimal hyperplasia as well as arterial remodelling result in flow-limiting renarrowing of the arterial lumen at the angioplasty site. Intimal hyperplasia is an important candidate for gene therapy since it is related to smooth muscle cell proliferation, which is an inviting target for molecular antiproliferative strategies. To date, adenoviral vectors are, by far, the most efficient vectors to perform in vivo arterial gene transfer. These vectors, as well as others, have been recently used to demonstrate that therapeutic genes encoding cytotoxic (herpes virus thymidine kinase) or cytostatic (hypophosphorylatable Rb, Gax, endothelial nitric oxide synthase) products successfully inhibit smooth muscle cell proliferation and related intimal hyperplasia. Despite substantial progress, major technical issues, including the toxicity of first-generation adenoviral vectors, inefficient transduction of atherosclerotic arteries, and the risk of extra-arterial transfection remain to be addressed before gene therapy is applied to clinical restenosis.
Feldman
L J
LJ
Department of Cardiology, Hôpital Bichat, Paris, France.
Tahlil
O
O
Steg
P G
PG
D000256:Adenoviridae / Q000235:genetics*; D017130:Angioplasty / Q000009:adverse effects; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D001158:Arteries / Q000293:injuries / Q000473:pathology; D002455:Cell Division / Q000235:genetics; D018014:Gene Transfer Techniques; D016161:Genes, Retinoblastoma / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000235:genetics; D055502:Secondary Prevention; D013937:Thymidine Kinase / Q000235:genetics
D019001:Nitric Oxide Synthase; D013937:Thymidine Kinase