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Monocytic cell adhesion to oxidised ligands: relevance to cardiovascular disease
Atherosclerosis, the major cause of vascular disease, is an inflammatory process driven
by entry of blood monocytes into the arterial wall. LDL normally enters the wall, and stimulates
monocyte adhesion by forming oxidation products such as oxidised phospholipids (oxPLs) and
malondialdehyde. Adhesion molecules that bind monocytes to the wall permit traffic of these cells.
CD14 is a monocyte surface receptor, a cofactor with TLR4 forming a complex that binds oxidised
phospholipids and induces inflammatory changes in the cells, but data have been limited for monocyte
adhesion. Here, we show that under static conditions, CD14 and TLR4 are implicated in adhesion
of monocytes to solid phase oxidised LDL (oxLDL), and also that oxPL and malondialdehyde (MDA)
adducts are involved in adhesion to oxLDL. Similarly, monocytes bound to heat shock protein 60
(HSP60), but this could be through contaminating lipopolysaccharide. Immunohistochemistry on
atherosclerotic human arteries demonstrated increased endothelial MDA adducts and HSP60, but
endothelial oxPL was not detected. We propose that monocytes could bind to MDA in endothelial
cells, inducing atherosclerosis. Monocytes and platelets synergized in binding to oxLDL, forming
aggregates; if this occurs at the arterial surface, they could precipitate thrombosis. These interactions
could be targeted by cyclodextrins and oxidised phospholipid analogues for therapy