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.

Automated summary

Atherosclerosis, the main cause of vascular disease, is an inflammatory process driven by monocyte entry into the arterial wall. This study demonstrates the role of CD14 and TLR4 in monocyte adhesion and highlights the involvement of oxidised phospholipids and malondialdehyde in adhesion to oxidised LDL. Additionally, the study suggests that monocytes may bind to MDA in endothelial cells, contributing to atherosclerosis. The interactions between monocytes and platelets in binding to oxLDL could potentially lead to thrombosis at the arterial surface, highlighting the importance of targeted therapeutic interventions.