LOCALIZATION AND ACTIVITY OF TISSUE FACTOR IN HUMAN AORTIC ATHEROSCLEROTIC LESIONS

Tissue factor (TF) is a transmembrane protein that serves as the major initiator of the blood coagulation cascade. The overexpression of TF antigen and mRNA has previously been reported in advanced atherosclero tic lesions. Recently TF procoagulant activity has also been identifie d in these lesions. However, localization and activity of TF in variou s stages of atherosclerosis have not yet been reported. We studied TF localization and its activity in three stages of the human atheroscler otic lesions (diffuse intimal thickening, fatty streak, and atheromato us plaque). The thoracic aortas were obtained from 23 autopsy cases an d were examined immunohistochemically using an anti-human TF polyclona l antibody and biotinylated factor VIIa (FVIIa) as a probe to test the FVIIa-binding ability of TF. In addition, the TF-mediated activation of factor X (FX) was quantitatively assessed using a chromogenic assay . In lesions of the diffuse intimal thickening and the fatty streak, a lmost all of intimal smooth muscle cells (SMCs), macrophages, and endo thelial cells were positive for TF. In the atheromatous plaques, TF an tigen was detected extensively in the extracellular matrix as well as in the intimal cells. TF in all stages of atherosclerotic lesions had the ability to bind biotinylated FVIIa. TF activity was detected in ea ch lesion and was more prominent in fatty streaks and atheromatous pla ques than in the diffuse intimal thickening. These results indicate th at active TF is expressed in the early stage of atherosclerotic lesion s as well as in the advanced stage, and it contributes to the thrombot ic property of human atherosclerotic lesions. (C) 1997 Elsevier Scienc e Ireland Ltd.