COLOCALIZATION OF FIBRINOLYTIC ACTIVATORS AND INHIBITORS WITH MACROPHAGES IN ATHEROSCLEROTIC VESSELS

The plasmin system is involved in hemostasis and tissue remodelling. T he accumulation of plasminogen activators and their inhibitors in athe rosclerotic lesions may be due to invasion of inflammatory cells in th e vessel wall. High concentrations of macrophages are associated with increased risk of atherosclerotic plaque rupture. By immunohistochemis try on circumferential serial sections of atherosclerotic and healthy vessels the morphological association of plasminogen activators and in hibitors with macrophages was studied. Urokinase plasminogen activator (u-PA), plasminogen activator inhibitor type 2 (PAI-2), and macrophag es were mainly expressed within plaques while tissue plasminogen activ ator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were al so expressed outside plaque lesions. Computer assisted image analysis on diseased vessels showed that regulatory proteins of the fibrinolyti c system were found more often in areas positive for macrophages than in other parts of the sections (p < 0.001). u-PA was significantly mor e defined to areas positive for macrophages than tissue plasminogen ac tivator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) (p < 0.05). Similarly, PAI-2 expression was more associated with macrophag e distribution than PAI-1 (p < 0.05). Tumor necrosis factor alpha (TNF alpha), an inflammatoric mediator of macrophages, had the same levels of co-localization with macrophages as u-PA and PAI-2. These results suggest that u-PA and PAI-2 might be key factors for inflammatory regu lation of plasmin mediated proteolysis in the vessel walls. (C) 1998 b y Elsevier Science Inc.