Neointima proliferation after coronary angioplasty is an unresolved problem in interventional cardiology. Local vascular gene therapy is an attractive approach to overcome this major clinical problem. The three candidate vectors adenovirus (AdCMV-beta gal), adeno-associated virus (AAV-beta gal) and liposomes were compared. Efficienies of transfection were compared in primary porcine smooth muscle cell culture (pSMC), human umbilical venous endothelial cell culture (HUVEC) and human ECV-304. The lacZ gene for beta-galactosidase was also delivered with a microporous ballon catheter in eighteen coronary arteries of nine different pigs. In all cell cultuer types adenoviral transfection led to a medium to high rate of expression. Adeno-associated virus led only to minimal expression. Liposomes led to minmal expression as well. In coronary arteries adenovirus led to high expression in endothelium, but also in adjacent myocardium. Adeno-associated virus did not lead to expresion in 14 days. Liposomal gene transfer achieved moderate transfection rates in endothelium and media. High expression in cell culture did not predict efficacy in animal models. Probably none of these vectors seem appropriate for local gene therapy in coronary arteries.
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Neointima proliferation after coronary angioplasty is an unresolved problem in interventional cardiology. Local vascular gene therapy is an attractive approach to overcome this major clinical problem. The three candidate vectors adenovirus (AdCMV-beta gal), adeno-associated virus (AAV-beta gal) and liposomes were compared. Efficienies of transfection were compared in primary porcine smooth muscle cell culture (pSMC), human umbilical venous endothelial cell culture (HUVEC) and human ECV-304. The...
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