Impact of Adenovirus-mediated Local Expression of Human Tissue Factor Pathway Inhibitor on Vascular Smooth Muscular Cell Proliferation and Apoptosis in the Stent-implanted Femoral Artery of the Rabbit

Abstract

This study examined the effect of gene transfer of local tissue factor pathway inhibitor (TFPI) on vascular smooth muscle cells (VSMCs) in stent-implanted arteries. Rabbit femoral arteries were balloon-injured, stent-implanted and infected with the replication-defective recombinant adenovirus-mediated TFPI gene (Ad-TFPI) or the β-galactosidase gene (Ad- LacZ), or treated with saline solution. Expression of TFPI at the site of the stent was confirmed after 3 days using reverse transcription-polymerase chain reaction (RT-PCR). After 7 days, proliferating cells were visualized by immunostaining with antibodies to proliferating cell nuclear antigen (PCNA) and apoptotic cells were detected using the terminal deoxynucleotidyl mediated nick end labelling (TUNEL) technique. Cell proliferation was significantly decreased and apoptosis significantly increased in the media in the Ad-TFPI group compared with the other two groups. In conclusion, Ad-TFPI gene transfer can significantly suppress VSMC proliferation and induce its apoptosis in the media at the site of an implanted stent and may have potential for the treatment of instent re-stenosis.