Arteriosclerosis and Thrombosis, Vol 11, 1821-1829, Copyright © 1991 by American Heart Association

ARTICLES

Stimulating effect of oxidized low density lipoproteins on plasminogen activator inhibitor-1 synthesis by endothelial cells

Y Latron, M Chautan, F Anfosso, MC Alessi, G Nalbone, H Lafont and I Juhan-Vague
Laboratory of Haematology, CHU Timone, Marseille, France.

Oxidized low density lipoproteins (ox-LDL) are thought to accelerate atherogenesis. It was recently demonstrated that patients with coronary heart disease have defects in plasma fibrinolysis due to increased plasminogen activator inhibitor-1 (PAI-1) levels. Investigation of PAI- 1 synthesis by endothelial cells may allow insight into the effect of native LDL (N-LDL) and ox-LDL on endothelial cells. In the present study, secretion of PAI-1 by human umbilical vein endothelial cells (HUVEC) in culture was evaluated after incubation with N-LDL and ox- LDL. Ox-LDL were obtained by peroxidation under ultraviolet radiation, which induced compositional changes in LDL, namely, a decrease in the levels of arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and alpha-tocopherol and an increase in the malondialdehyde content. Ox-LDL induced a dose-dependent increase in PAI-1 secretion by HUVEC as assayed by an enzyme-linked immunosorbent assay. After a 24- hour incubation, a twofold increase in the PAI-1 content was observed with 50 micrograms/ml ox-LDL protein. Studies with inhibitors of protein synthesis and metabolic labeling with [35S]methionine confirmed that PAI-1 synthesis was stimulated by ox-LDL. N-LDL had no detectable effect on PAI-1 secretion. Binding studies with radiolabeled lipoproteins showed that the effect of ox-LDL was independent of the B/E receptor. Our experiments indicate that ox-LDL stimulate PAI-1 secretion from HUVEC and that this effect may involve a scavenger receptor.

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