Neointimal growth can be influenced by local adventitial gene manipulationvia a needle injection catheter

Revascularization by percutaneous transluminal coronary angioplasty is limi ted in the long-term by restenosis, which is luminal renarrowing in the fir st 6 months after the procedure. Smooth muscle cell proliferation is though t to be an important factor in restenosis; this leads to neointima formatio n and arterial lumen narrowing. Local therapy delivered perivascularly may have an effect on events in the neointima and reduce restenosis. The effect of delivering expression vector plasmids for senescent cell-derived inhibi tor SDI-1, which regulates cell proliferation, and its antisense, into the perivascular tissue of injured arteries was investigated in a porcine arter ial injury model using a needle injection catheter. Transfection efficiency , biological effect and plasmid dissemination were evaluated in arterial an d organ tissue sections between 2 days and 4 months. A limited number of ad ventitial, medial and neointimal cells were transfected up to 4 months. sdi gene transfer did not result in a change in neointima. Transfer of antisen se sdi resulted in an increase in neointima after 3 weeks. No DNA plasmid w as detected in control tissues. Liposomally-mediated adventitial local gene delivery is feasible and safe using the needle injection catheter in a por cine model. A limited number of cells was transfected, with expression of t ransfected genes up to 4 months after delivery. A transient biological effe ct with increased neointima was observed after delivery of the antisense sd i gene. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.