Prevention of restenosis using the gene for cecropin complexed with DOCSPER liposomes under optimized conditions

Abstract

Up to 30% of patients undergoing coronary angioplasty develop a renarrowing of treated vessels following percutaneous transluminal coronary angioplasty with or without stent implantation, called restenosis. Smooth muscle cell proliferation, among other mechanisms, is an important factor in restenosis leading to neointima formation and consequent arterial lumen narrowing. Cecropins are antimicrobial peptides with antiproliferative properties in mammalian cells which have been shown to suppress neointimal formation. In this investigation, a plasmid carrying the gene for pre-pro-cecropin A, complexed with new generation liposomes optimized for transfer conditions for vascular cells was delivered to the adventitia of arteries in a porcine arterial injury model using a needle injection catheter. Retention of the plasmid in treated arteries was demonstrated for at least 21 days following delivery. Whereas previous experiments using first generation liposomes demonstrated significant but not complete neointima inhibition, the use of new liposomes under optimized conditions resulted in almost total suppression of neointimal proliferation. Thus, in vivo gene transfer of cecropins may be therapeutically applicable in restenosis prevention.