Gene therapy of fibroproliferative vasculopathies: current ideas in molecular mechanisms and biomedical technology

Abstract

Intimal hyperplasia occurs primarily as a part of the pathogenesis of coronary artery disease or secondary to therapeutic intervention in relieving vascular occlusion. Intimal hyperplasia involving vascular smooth muscle cells is found in atherosclerosis, post-balloon angioplasty restenosis, in-stent restenosis and vein graft disease, predominantly involving the use of saphenous vein conduits in coronary artery bypass grafting procedures. One potentially exciting area is that of gene therapy. Gene and protein expression patterns at the site of vasculoproliferative lesions have been widely studied and several target areas have been identified on the basis of whether the gene has an antiproliferative, proapoptotic, matrix degrading or endothelial protective action. Blood vessels are easily accessible for the delivery of the gene product, and experimental studies using animal models have used catheter-delivered gene products at the site of vascular injury. Currently, the application of antisense technology and adenoviral vector-mediated delivery has shown significant promise, albeit in in vitro or animal model settings. In this review, we discuss the current knowledge in the application of gene therapy in fibroproliferative vasculopathies. We examine some of the cellular mechanisms and intermediaries which could be potential candidates for gene targeting. We also present some of the advances in biomedical technology that might provide useful vehicles for pinpoint delivery of the gene product. Could the future of restenosis treatment be in gene therapy or is it misplaced enthusiasm?