Atherosclerotic plaque and tissue factor

Rupture of the atherosclerotic plaque is closely related to thrombus formation and subsequent ischemic disease, such as acute coronary syndrome. However, the mechanism of thrombus formation after plaque rupture is not well understood. We examined the immnohistochemical localization of tissue factor (TF) in the human atherosclrotic lesion with monoclonal antibody against human TF. We also examined TF activity in the atherosclerotic intima that is experimentally induced by cholesterol feeding in rabbits, and in the coculture system of human umbilical vein endothelial cells (HUVEC) and human peripheral blood monocytes (PBMC) which are stimulated by oxidized LDL. TF was mainly localized in the foam cells, most of which are derived from macrophages, and its localization is well correlated with that of fibrin. Less amount of TF was also seen in the extracellular matrix. Experimentally induced atherosclerotic intima showed TF activity more intensely than non-atherosclerotic intima. The TF activity was thought to be derived from subendothelial tissue which was full of foamy macrophages, as scanning electron microscopy demonstrated exposure of subendothelial tissue. In vitro studies revealed that oxidized LDL stimulated TF activity in coculture of HUVEC and PBMC and that this stimulation required direct contact between the two cells. These findings suggest that TF localizing in atherosclerotic intima plays an important role not only in fibrin formation within atherosclerotic plaque but also in thrombus formation at the rupture site of plaque.