TISSUE FACTOR PATHWAY INHIBITOR EXPRESSION IN ATHEROSCLEROSIS

Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of tissue factor (TF)-initiated coagulation and may play a role in regulating c oagulation in atherosclerotic plaques. The expression of TFPI protein and mRNA was examined by immunohistology and in situ hybridization in normal human and rabbit arteries, in human carotid arteries with advan ced atherosclerosis, and in atherosclerotic aortas from cholesterol-fe d rabbits. In normal human and rabbit arteries, TFPI protein and mRNA were detected in the adventitial layer but were undetectable in the lu minal endothelium. In the medial smooth muscle layer of rabbits, weak expression of TFPI mRNA, but not protein, was detected; in that of hum ans, neither TFPI mRNA nor protein was detectable. In atherosclerotic arteries, TFPI protein and mRNA were detected in three of six internal carotid plaques from patients. undergoing endarterectomy, and mRNA al one was detected in one further specimen. TFPI protein was found in ar eas of the plaque where TF was abundant and colocalized with macrophag es, suggesting that these cells are responsible for TFPI synthesis. TF PI protein and mRNA were also detected in fatty-streak lesions in 18 o f 19 rabbits fed a high-cholesterol diet for periods between 4 and 16 weeks. In these macrophage-rich lesions, expression of TFPI protein an d mRNA was most intense at the base of the plaques. These studies sugg est that TFPI is expressed in the adventitial layer of large arteries and that in atherosclerotic vessels, TFPI is expressed by macrophages in focal areas throughout the plaque. Local production of TFPI may reg ulate procoagulant activity and thrombotic events within atherosclerot ic plaques.