Liposome-CAT complexes induce development of a non-inflammatory neointimal lesion in rabbit carotid arteries

Abstract

Liposomes are attractive vectors for intraarterial cardiovascular applications because they can deliver genes into the quiescent cells of an intact vessel wall. In a model of in vivo intraarterial gene transfer in uninjured rabbit carotid arteries, we found that cationic liposomes complexed to the CAT reporter gene induced formation of an intimal lesion in rabbit arteries. Interestingly, unlike the lesions induced by viral vector gene transfer, this lesion is non-inflammatory, composed only of smooth muscle cells without evidence of leukocyte infiltration. Carotids transfected with liposomes complexed to the plasmid vector alone, liposomes complexed to the eukaryotic gene encoding human endothelial nitric oxide synthase, and sham-operated controls all evidenced only minimal lesions. We postulate that CAT DNA, perhaps through bacterial DNA CpG motifs or, less likely, the CAT protein itself may be inducing smooth muscle cell proliferation in the arterial walls transfected with the CAT-liposome complexes. These observations should be taken into account in other long-term in vivo vascular gene delivery models utilizing CAT as a reporter gene.