| |
Tissue factor pathway inhibitor
(TFPI) is a potent inhibitor of tissue factor (TF) -initiated coagulation
and may play a role in regulating coagulation 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 advanced atherosclerosis, and in atherosclerotic aortas
from cholesterol-fed rabbits. In normal human and rabbit arteries, TFPI
protein and mRNA were detected in the adventitial layer but were undetectable
in the luminal endothelium. In the medial smooth muscle layer of rabbits,
weak expression of TFPI mRNA, but not protein, was detected; in that of
humans, 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 alone was detected
in one further specimen. TFPI protein was found in areas of the plaque where
TF was abundant and colocalized with macrophages, suggesting that these
cells are responsible for TFPI synthesis. TFPI protein and mRNA were also
detected in fatty-streak lesions in 18 of 19 rabbits fed a high-cholesterol
diet for periods between 4 and 16 weeks. In these macrophage-rich lesions,
expression of TFPI protein and mRNA was most intense at the base of the
plaques. These studies suggest 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 regulate procoagulant activity and thrombotic events within atherosclerotic
plaques. |
