Abstract
BackgroundBlood 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.Methods and ResultsWe 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.ConclusionOur 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.
Highlights
Atherosclerosis is a clinical condition for which multiple genetic and environmental causal factors have been proposed
Our data help complete the paradigm of atherosclerosis: Modified LDL locally enhances fibrin deposition; fibrin deposits enhance endothelial permeability; this effect allows subendothelial accumulation of lipid and foam cells
Fibrinolytic Process at the Cell Surface EA.hy926 endothelial cells and primary human smooth muscle cells (SMCs) were inoculated on semiporous PET membranes located inside cuvettes adapted to the lysis timer, and grown to confluence
Summary
Atherosclerosis is a clinical condition for which multiple genetic and environmental causal factors have been proposed. The atherosclerotic process involves thickening of the arterial wall; this thickening is related to the accumulation of foam cells, macrophages that have engulfed large amounts of modified LDL particles. These macrophages differentiate from monocytes that are recruited to the endothelium and activated to express leukocyte adhesion molecules [1,2]. These adhesins are themselves induced by modified LDLs (more abundant in patients with hypercholesterolemia), and it is, widely accepted that they are involved in atherogenesis [3]. We investigated the role of pericellular myeloperoxidase oxidized LDLs (Mox-LDLs) in this balance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
