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Expression of tissue factor pathway inhibitor-2 (TFPI-2), which has anticoagulant and antiproliferative activities, is decreased in abdominal aortic aneurysm (AAA). The purpose of this study was to determine whether gene transfer of TFPI-2 would reduce AAA formation in a rat model of AAA. Rats received an endothelial-denuded segment of the abdominal aorta from New Zealand white rabbits and were infused retrogradely via the carotid artery with adenoviral vector encoding TFPI-2 (Ad-TFPI-2). The animals were sacrificed at 7 days and 28 days after the arterial interposition graft, and the aortas were analyzed for the presence of AAA. Aortic arch aneurysms were observed in 9 of 15 (60%) rats after 28 days. In contrast, adenoviral gene transfer significantly reduced the incidence of AAA formation at 28 days (P=0.003). TFPI-2 expression was confirmed by real-time reverse-transcription polymerase chain reaction, Western blotting, and flow cytometry. The AAA formation that did occur was significantly smaller in the Ad-TFPI-2-treated rats than in control rats (P=0.02). These findings suggest that gene transfer of TFPI-2 reduces AAA formation in a rat model of AAA and may serve as a 0b46394aab
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