Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty

Blood vessels are among the easiest targets for gene therapy, However, no d ata are available about the safety and feasibility of intracoronary gene tr ansfer in humans. We studied the safety and efficacy of catheter-mediated v ascular endothelial growth factor (VEGF) plasmid/liposome (P/L) gene transf er in human coronary arteries after percutaneous translumenal coronary angi oplasty (PTCA) in a randomized, double-blinded, placebo-controlled study. T he optimized angioplasty/gene delivery method was previously shown to lead to detectable VEGF gene expression in human peripheral arteries as analyzed from amputated leg samples. Gene transfer to coronary arteries was done wi th a perfusion-infusion catheter, using 1000 mu g of VEGF or beta-galactosi dase plasmid complexed with 1000 mu l of DOTMA:DOPE liposomes, Ten patients received VEGF P/L, three patients received beta-galactosidase P/L, and two patients received Ringer lactate. Gene transfer to coronary arteries was f easible and well tolerated. Except for a slight increase in serum C-reative protein in all study groups, no adverse effects or abnormalities in labora tory parameters were detected. No VEGF plasmid or recombinant VEGF protein was present in the systemic circulation after the gene transfer. In control angiography 6 months later, no differences were detected in the degree of coronary stenosis between treatment and control groups. We conclude that ca theter-mediated intracoronary gene transfer performed after angioplasty is safe and well tolerated and potentially applicable for the prevention of re stenosis and myocardial ischemia.