Update on gene therapy for intimal hyperplasia

Trauma to the vessel wall leads to smooth muscle cell (SMC) activation and eventual intimal hyperplasia. This process occurs in restenosis following balloon angioplasty, particularly with stent placement, occlusion of vascular bypasses, and arteriopathy of chronic allograft rejection. Genetic interventions affecting the cell cycle or early postinjury events have been successful in limiting SMC proliferation in vitro and in animal models. Gene therapy strategies have included the use of antisense oligonucleotides to block protein synthesis, transduced genes to cause cytotoxicity, and genetically engineered cells to decrease the response to injury. The clinical application of gene therapy in vascular diseases should follow the evolution of delivery systems that enable efficient local gene transfer to the arterial wall. (Tab. 1, Fig. 1, Ref. 30.)