Does lipoprotein(a) (Lp(a)) complete with plasminogen in human atherosclerotic lesions and thrombi?

Thrombotic occlusion is the major cause of myocardial infarction (MI), and fibrin accumulation appears to play a significant role in development of atherosclerotic lesions. Any factor that reduces the lysis of fibrin may thus increase the risk of MI, and it has been suggested that this accounts for the atherogenicity of the lipoprotein variant Lp(a). The characteristic feature of Lp(a) is an apoprotein which is homologous with part of the plasminogen molecule, and experiments in vitro suggest that it interferes with uptake and activation of plasminogen on cell surfaces and fibrin. The presence of Lp(a) also seemed to offer an explanation for the apparent absence of plasminogen from 70-80% of intimal samples. We have compared the levels of Lp(a) and plasminogen in normal intima and atherosclerotic lesions. In aortic intima there was no relation between Lp(a) and plasminogen, which was absent in some samples with no Lp(a), and present in others with high levels. In intravascular thrombi plasminogen was present at a rather constant concentration (16.3 +/- 4.6 micrograms/100 mg wet tissue), whereas Lp(a) varied over a 100 fold range (0-104 micrograms/100 mg). Plasminogen binds to fibrin and is activated on the fibrin clot, so levels in extracts may not fully represent Lp(a)/plasminogen interactions. After extraction the residual tissues and thrombi were treated with 1 M epsilon-aminocaproic acid (epsilon-aca) to elute lysine-bound components. Lp(a) was eluted from all but one intimal sample, confirming previous findings on its binding to fibrin in lesions, but there was no relation between the amounts of Lp(a) and plasminogen in the tissue eluates. Paradoxically, in the thrombi there was a weak positive correlation between Lp(a) and plasminogen in epsilon-aca eluates (r = 0.504, P = 0.05). These results do not support the hypothesis that Lp(a) displaces plasminogen in vivo, but the large amount of Lp(a) eluted by epsilon-aca suggests that its atherogenicity resides in preferential binding to fibrin, leading to increased lipid accumulation in lesions.