Gene inhibition and gene augmentation for the treatment of vascular proliferative disorders.

ABSTRACT

Gene therapy is emerging as a potential strategy for the treatment of vasculoproliferative diseases such as restenosis after angioplasty, vascular bypass graft occlusion and transplant coronary vasculopathy for which no known effective therapy exists. Our laboratory has demonstrated that vascular smooth muscle proliferation and lesion formation can be prevented by the blockade of genes regulating cell cycle progression. With this approach it was also shown that genetically engineered bioprostheses can be developed that are resistant to accelerated atherosclerosis and thus to graft failure. We have also reported that the direct in vivo transfer of a cDNA encoding endothelial nitric oxide synthase resulted in inhibition of neointimal lesion formation and improvement of vascular reactivity, demonstrating that therapeutic effects can also be achieved by the in vivo transfer of gene(s) whose product(s) exert a paracrine effect on the vessel wall.