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This study was undertaken to determine if the fibrinolytic capacity of the intimal-medial layer of the human aorta decreases with increasing severity of atherosclerosis. Aortas were obtained from 32 normal healthy subjects who died from a sudden traumatic incident. Paired controls consisted of samples of grossly healthy tissue which were removed from sites adjacent to the plaque. Intima and media containing atherosclerotic lesions and lesion free control sections were stripped from the thoracic aorta and were homogenized. Plasminogen, α2-macroglobulin and α1-antitrypsin levels in the homogenate supernatants were determined by radial immunodiffusion. Plasmin activity was determined on plasminogen free fibrin plates. No significant differences were found in the content of any of the moieties measured between the paired control intima-media and the lesions. The plasminogen content of the intima-media did not change as a function of the lesion grade; however, the streptokinase activated plasmin, as measured by fibrinolysis on fibrin plates, was decreased six times in tissue containing lesions of grades 4-6 when compared to lesions of grades 1 and 2. The mean age of both groups was not significantly different. In these same samples the plasmin inhibitors α2 macroglobulin and α1-antitrypsin were increased 3 times and 2 times, respectively in the intima-media of the aortas containing grade 4-6 lesions as compared to the aortas containing grade 1 plus 2 lesions. These data suggest that there is a decreased fibrinolytic capacity of the normal intimamedia of aortas containing lesions of grade 4-6. This decrease in plasmin activity is not due to a decrease in amounts of plasminogen but rather to an increase in α2- macroglobulin, α1-antitrypsin, and possibly other plasmin inhibitors.

Quantitative Studies On The Fibrinolytic Activity Of Normal Intima And Atherosclerotic Plaque