Exposure of endothelial cells to physiological levels of myeloperoxidase-modified LDL delays pericellular fibrinolysis.
BACKGROUND
Blood fluidity is maintained by a delicate balance between coagulation and fibrinolysis. The endothelial cell surface is a key player in this equilibrium and cell surface disruptions can upset the balance. We investigated the role of pericellular myeloperoxidase oxidized LDLs (Mox-LDLs) in this balance.


RESULTS
We designed a technical device that enabled us to monitor fibrinolysis in real-time at the surface of an endothelial cell line (EA.hy926), and showed that Mox-LDL decreased pericellular fibrinolysis. There were no changes in fibrinolysis when EA.hy926 endothelial cells were exposed to native LDL (24 hours) at doses of 10, 50, 100 and up to 1250 µg/ml. However, treatment of EA.hy926 endothelial cells with 10 and 50 µg/ml of Mox-LDL (physiological serum concentrations) increased the lysis time by 15 and 13%, respectively (p<0.001), although this effect was not present at higher concentrations of 100 µg/ml. This effect was not correlated with any changes in PAI-1 or t-PA or PA Receptor (PAR) expression. No effect was observed at the surface of smooth muscle cells used as controls.


CONCLUSIONS
Our data link the current favorite hypothesis that modified LDL has a causal role in atheroma plaque formation with an old suggestion that fibrin may also play a causal role. Our data help complete the paradigm of atherosclerosis: Modified LDL locally enhances fibrin deposition (present work); fibrin deposits enhance endothelial permeability; this effect allows subendothelial accumulation of lipid and foam cells.
Experimental Medicine Laboratory, Université Libre de Bruxelles 222 Unit, CHU Charleroi, A. Vésale, Montigny-Le-Tilleul, Belgium. karim.zouaoui@chu-charleroi.be
Karim
K
Zouaoui Boudjeltia
Jalil
J
Daher
Pierre
P
Van Antwerpen
Nicole
N
Moguilevsky
Paul
P
Delree
Jean
J
Ducobu
Martine
M
Raes
Bassam
B
Badran
Michel
M
Vanhaeverbeek
Dany
D
Brohee
Claude
C
Remacle
Luc
L
Vanhamme
D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009195:Peroxidase / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase