The localization of tissue factor and apolipoprotein(a) in atherosclerotic lesions of the human aorta and their relation to fibrinogen-fibrin transition

Abstract

We examined the immunohistochemical distribution of tissue factor (TF), apolipoprotein (a) (apo(a)) in atherosclerotic intimas of human thoracic aortas obtained from 51 autopsies in order to analyze the mechanism of fibrinogen-fibrin transition as a part of thrombogenic properties of atherosclerotic intimas. TF was overexpressed mainly by macrophages in both fatty streaks and more advanced lesions, while it was also scatteringly deposited in the matrix of advanced lesions, especially in the atheromatous gruel. TF-positive macrophages were frequently intermingled at the base of fibrin thrombi formed on the eroded intimas. On the other hand, apo(a) was localized in the stroma and within some macrophages, and also in the mural thrombi. Fibrinogen and fibrin were more frequently detected in the matrix of advanced lesions than in that of early lesions. Fibrin was occasionally co-located with cell- and matrix-associated TF and apo(a) deposited in matrix. These findings suggest that the overexpressed TF in the atherosclerotic intima plays a critical role in the initiation of fibrin formation. This could result from either fibrinogen permeating into the intima or from rupture of the fibrous cap overlying atheromas. Apo(a) deposited in the atherosclerotic intima may also participate in the persistent deposition of fibrin.