[Ad-TFPI gene transfer attenuates intimal proliferation in rabbit carotid arteries after balloon injury].

ABSTRACT

OBJECTIVE: To investigate the in vivo gene expression of adenovirus-mediated human tissue factor pathway inhibitor (hTFPI) and its inhibition effects on intimal proliferation in rabbit carotid arteries after balloon injury. METHODS: Rabbits underwent carotid artery balloon injuries were treated with Ad-TFPI (n = 25), Ad-LacZ (n = 25) or PBS (n = 10), respectively. Sham operated rabbits (n = 10) serve as normal controls. The expressions of human TFPI at mRNA and protein levels were detected by RT-PCR and ELISA respectively on the 3rd, 7th, 10th, 14th, 28th day after operation. Intimal proliferation was detected by angiograms and morphometric analysis. RESULTS: TFPI mRNA and protein expressions were detected at 3 days and peaked at the 10th and 14th day after TFPI gene transfer. The expressions were still detectable on the 28th day. There was no TFPI expression in Ad-LacZ group. The carotid angiogram results indicated that the minimal lumen diameter in TFPI group was significantly larger and the lumina stenosis percentage was significantly lower in TFPI group compared those in Ad-LacZ and PBS groups (all P < 0.05). The morphometric analysis showed that the intimal area, the ratio of the intimal/media area, the lumina stenosis percentage in TFPI group were all significantly reduced compared with those in Ad-LacZ and PBS groups (all P < 0.01). CONCLUSIONS: The TFPI gene could be effectively transferred by adenovirus vector to injured carotid arteries and transferred Ad-TFPI could significantly attenuate intimal proliferation in balloon injured carotid arteries in rabbits.