Stimulating effect of oxidized low density lipoproteins on plasminogen activator inhibitor-1 synthesis by endothelial cells.
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.
Laboratory of Haematology, CHU Timone, Marseille, France.
Y
Y
Latron
M
M
Chautan
F
F
Anfosso
M C
MC
Alessi
G
G
Nalbone
H
H
Lafont
I
I
Juhan-Vague
D001667:Binding, Competitive; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000378:metabolism*; D013997:Time Factors
D008077:Lipoproteins, LDL; D010545:Peroxides; D015849:Plasminogen Inactivators