Inhibition of tissue factor reduces thrombus formation and intimal hyperplasia after porcine coronary angioplasty

OBJECTIVES We investigated the in vivo effects of tissue factor (TF) inhibi tion with recombinant tissue factor pathway inhibitor (rTFPI) on acute thro mbus formation and intimal hyperplasia and the in vitro effects on smooth m uscle cell migration and proliferation. BACKGROUND Inhibition of TF with TFPI has been shown to reduce intimal hype rplasia in experimental models. However, its effects after coronary angiopl asty and the cellular mechanisms involved have not been investigated. METHODS Twenty-three swine underwent multivessel coronary angioplasty. Fift een (n = 25 arteries) were euthanized at 72 h to assess thrombus formation and eight (n = 24 arteries) at 28 days to assess intimal hyperplasia. Anima ls in the 72-h time point received: 1) human rTFPI (0.5 mg bolus plus 25 mu g/kg/min continuous infusion for 3 days) plus heparin (150 IU/kg intravenou s bolus) plus acetyl salicylic acid (ASA) (325 mg/day); 2) rTFPI regimen pl us ASA and 3) heparin (150 IU/kg intravenous bolus) plus ASA. RESULTS On histology the control group had evidence of mural thrombus (area 0.8 +/- 0.4 mm(2)). Treatment with TFPI plus heparin abolished thrombus fo rmation (mean area: 0.0 +/- 0.0 mm(2), p < 0.05) but was associated with pr olonged activated partial thromboplastin time and extravascular hemorrhage. Recombinant TFPI alone inhibited thrombosis without bleeding complications (mean area: 0.03 +/- 0.02 mm(2), p < 0.05 vs. control). Animals in the 28- day time point received continuous intravenous infusion of rTFPI or control solution for 14 days. Tissue factor pathway inhibitor reduced neointimal f ormation with mean intimal area of 1.2 +/- 0.3 mm2 versus 3.2 +/- 0.4 mm2 i n the control group; p < 0.01. Recombinant TFPI had no effect on human aort ic smooth muscle cell growth but inhibited platelet-derived growth factor B E-induced migration. CONCLUSIONS Inhibition of TF with rTFPI can prevent acute thrombosis and in timal hyperplasia after injury. Tissue factor plasma inhibitor may prove us eful as an adjunct to intracoronary interventions. (C) 2000 by the American College of Cardiology.