Abstract
Thrombus formation is frequently associated with atherosclerotic lesions, and thrombus formation on coronary plaque rupture or erosion plays a key role in the pathogenesis of acute coronary syndrome. Tissue factor (TF) is a major initiator of the blood coagulation cascade. Overexpression of the TF antigen and mRNA has been found in atherosclerotic plaques and atherectomy specimens. We examined the morphology of intimal injury and localization of the TF antigen in human aortic and coronary atherosclerotic lesions, and in the rabbit aorta. In human atherosclerotic lesions (diffuse intimal thickening, fatty streak, and atheroma), intimal smooth muscle cells (SMCs), macrophages and some endothelial cells were positive for TF. In addition, in atheromatous plaques, the TF antigen was also detected in the extracellular matrix. These atheromatous lesions showed a high TF activity by a chromogenic assay using S-2222. In coronary atherosclerotic lesions, SMCs and endothelial cells were strongly and macrophages were weakly positive for TF. We experimentally made three types of atherosclerotic lesions (diffuse intimal thickening, fatty intimal thickening and fibrofatty plaque) in rabbit aortas by balloon catheter and cholesterol diet. In these atheromatous lesions, SMCs, endothelial cells and extracellular matrix were strongly and macrophages were weakly positive for TF. When the diffuse intimal thickening and fibrofatty plaques were injured by a balloon catheter, fibrin-rich thrombus formation was observed. On the other hand, when fatty intimal thickening lesions were injured, platelet rich thrombus formation was observed. These findings suggest that TF in atherosclerotic lesions plays an important role in thrombus formation not only at the plaque rupture site but also at the plaque erosion site.
