Journal Article

Exposure of Endothelial Cells to Physiological Levels of Myeloperoxidase-Modified LDL Delays Pericellular Fibrinolysis

Van Antwerpen, Pierre, Raes, Martine, Zouaoui Boudjeltia, Karim, Vanhamme, Luc, Vanhaeverbeek, Michel, Moguilevsky, Nicole, Remacle, Claude, Delree, Paul, Badran, Bassam, Brohee, Dany, Ducobu, Jean, Daher, Jalil

2012

Overview

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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Angina pectoris / Angiogenesis / Arteriosclerosis / Atherosclerosis / Biochemistry / Biology / Cell Membrane - drug effects / Cell Membrane - metabolism / Cell surface / Cellular biology / Coagulation / Endothelial cells / Endothelium / Fibrin / Fibrinolysis / Fibrinolysis - drug effects / Fluidity / Foam / Foams / Gene expression / Human Umbilical Vein Endothelial Cells - drug effects / Human Umbilical Vein Endothelial Cells - metabolism / Humans / Immunology / Laboratories / Lipoproteins (low density) / Lipoproteins, LDL - metabolism / Low density lipoprotein / Low density lipoproteins / Lysis / Medicine / MOX / Muscles / Myocytes, Smooth Muscle - drug effects / Myocytes, Smooth Muscle - metabolism / Parasitology / Permeability / Peroxidase / Peroxidase - pharmacology / Pharmacy / Physiological aspects / Physiology / Polyamide-imides / Proteins / Smooth muscle / Studies / Tumor Necrosis Factor-alpha - pharmacology