Abstract
ENDOTHELIAL cells play a critical role in thromboregulation by virtue of a surface-connected fibrinolytic system. Cultured endothelial cells synthesize and secrete tissue-type plasminogen activator (t-PA)1 which can bind to at least two discrete sites on the cell surface2–4. These binding sites preserve the catalytic activity of t-PA and protect it from its physiological inhibitor (PAI-1)2. N-terminal glutamic acid plasminogen (Glu-PLG), the main circulating fibrinolytic zymogen, also interacts specifically with the endothelial cell surface5,6. Binding is associated with a 12-fold increase in catalytic efficiency of plasmin generation by t-PA5 which may reflect conversion of Glu-PLG to its plasmin-modified form, N-terminal lysine plasminogen (Lys-PLG)7. Lipoprotein(a) is an atherogenic8–11 lipoprotein particle which contains the plasminogen-like12,13apolipoprotein(a) bound to low density lipoprotein. We report here that lipoprotein(a) interferes with endothelial cell fibrinolysis by inhibiting plasminogen binding and hence plasmin generation. In addition, we demonstrate lipoprotein(a) accumulation in atherosclerotic lesions. These findings may provide a link between impaired cell surface fibrinolysis and progressive atherosclerosis.
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Hajjar, K., Gavishi, D., Breslow , J. et al. Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature 339, 303–305 (1989). https://doi.org/10.1038/339303a0
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DOI: https://doi.org/10.1038/339303a0
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