Thromboresistance of balloon-injured porcine carotid arteries after local gene transfer of human tissue factor pathway inhibitor

Background-Tissue factor pathway inhibitor (TFPI) is an endogenous inhibito r of factor Xa and the coagulant initiator complex tissue factor/factor VII a. Methods and Results-To study the effects of TFPI gene transfer on thrombus formation, balloon-injured porcine carotid arteries were treated locally wi th an adenovirus encoding human TFPI (Ad-TFPI) or control virus. Gene trans fer of TFPI was confirmed by detection of human TFPI in the conditioned med ium of porcine carotid arteries kept in culture after in vivo transduction, When carotid flow was measured with Doppler probe 5 days after surgery, cy clic flow variations (CFVs) developed in 7 of 8 control pigs after constric tion of the injured carotid artery by 40%, and all control-treated arteries occluded after 70% constriction. In contrast, CFVs were observed in only 1 of 8 Ad-TFPI-treated pigs after 40% constriction, and only 3 of 8 occluded after constriction by 70% (P=0.0027 and P=0.007, respectively). None of th e 5 TFPI-transduced arteries open after 70% constriction developed CFVs dur ing an incremental epinephrine infusion. Conclusions-Compared with baseline, systemic hemostatic variables and plate let aggregation were unimpaired, suggesting that TFPI gene transfer can pre vent arterial thrombosis in the presence of severe shear stress and without detectable hemostatic impairment.