PLASMINOGEN-ACTIVATOR SYSTEM IN HUMAN CORONARY ATHEROSCLEROSIS

Altered coronary artery expression of plasminogen activator (PA) syste m components may predispose to thrombosis and modulate the Vascular re sponse to injury. By immunohistochemistry, we studied the expression o f PAs (tPA and uPA), their major physiological inhibitor (PAI-1), and a receptor for uPA (uPAR) in human coronary arteries with either pure fibrointimal proliferation (n=15) or developed atherosclerotic plaques (n=10). Overall, the degree of staining showed the following rank ord er: PAI-1>tPA>uPAR>uPA. A similar pattern was seen in two normal coron ary arteries. There were no significant differences in the extent of s taining in any vascular compartment between atherosclerotic arteries a nd those with only fibrointimal proliferation. However, the ratio of i ntimal to medial expression of tPA (P=.001) and uPAR (P=.004) was sign ificantly increased in atherosclerotic arteries, with a similar trend for uPA (P=.069) but not for PAI-1 (P=.73). Four of 10 atherosclerotic arteries had higher uPAR expression in the intima than in the media, whereas none of the 15 arteries with only fibrointimal proliferation h ad this pattern (P<.01). Dual labeling studies demonstrated colocaliza tion of all four PA system components in endothelial cells, smooth mus cle cells, and macrophages, with a predominance of PAI-1. Thus, corona ry arteries with a wide range of vascular pathology express an abundan ce of antifibrinolytic potential with enhanced local expression of pro fibrinolytic proteins, mainly within atherosclerotic plaques.