INHIBITORS OF FIBRINOLYSIS ARE ELEVATED IN ATHEROSCLEROTIC PLAQUE

The proteins of the fibrinolytic system have been examined in the huma n normal and atherosclerotic arterial wall by immunohistochemical tech niques and by quantitative immunoassay of extracts. The concentration of plasminogen activator inhibitor-1 (PAI-1) increased significantly d uring the progression from normal vessels to fatty streaks to the deve loped atherosclerotic plaque. Staining for PAI-1 was strongly positive , particularly in the areas adjacent to the plaque. In these areas, PA I-1 appeared to be colocalized with its binding protein vitronectin. a lpha(2)-Antiplasmin (alpha(2)-AP) was present in the aorta at even hig her concentrations than PAI-1; a small but significant increase was se en in some atherosclerotic compared with normal vessel walls. Tissue p lasminogen activator (TPA) showed the opposite trend, being lowest in lesions with plaque. Thus, higher concentrations of the two principal inhibitors of fibrinolysis, PAI-1 and alpha(1)-AP, together with lower levels of TPA, are characteristic of advanced atheromatous lesions. A lteration in the balance of the fibrinolytic system, favoring its inhi bition, may predispose to the development or maintenance of atheroscle rotic plaque.