Catheter-Mediated Vascular Endothelial Growth Factor Gene Transfer to Human Coronary Arteries after Angioplasty

Abstract

Blood vessels are among the easiest targets for gene therapy. However, no data are available about the safety and feasibility of intracoronary gene transfer in humans. We studied the safety and efficacy of catheter-mediated vascular endothelial growth factor (VEGF) plasmid/liposome (P/L) gene transfer in human coronary arteries after percutaneous translumenal coronary angioplasty (PTCA) in a randomized, double-blinded, placebo-controlled study. The 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 with a perfusion-infusion catheter, using 1000 microg of VEGF or beta-galactosidase plasmid complexed with 1000 microl 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 feasible and well tolerated. Except for a slight increase in serum C-reative protein in all study groups, no adverse effects or abnormalities in laboratory 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 catheter-mediated intracoronary gene transfer performed after angioplasty is safe and well tolerated and potentially applicable for the prevention of restenosis and myocardial ischemia.

High efficiency transduction of human VEGF165 into human skeletal myoblasts: in vitro studies

“…Attempts have also been made for site-specific catheter based delivery of angiogenic vectors for enhanced neovascularization (Laitinen et al, 2000). Apart from the conventional methods, implantation of genetically engineered cells is gaining popularity these days due to its promise in tissue engineering to repair damaged myocardium secondary to myocardial infarction .…”

The Role of Vascular Endothelial Growth Factor in Wound Healing

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10-year safety follow-up in patients with local VEGF gene transfer to ischemic lower limb

“…Valentis Inc., Burlingame, CA, USA) and mixing with 1000 ml Ringer's solution. 33 Plasmids and adenoviruses were tested to be free of any microbiological contaminants and endotoxin (o20 EU/dose, Whittaker, Walkersville, MD, USA). Selective digital subtraction angiography and intravascular ultrasound were conducted as described.…”