Oxidized LDL specifically promotes monocyte post-adhesion dynamics on endothelium, but not invasion itself at junctions, or subendothelial migration after invasion.

Abstract

Oxidized LDL has been reported to activate vascular endothelial cells and promote monocyte transmigration through endothelium, but the direct evidence for the effect of oxidized LDL on the process has not been fully addressed. Using HUVECs (Human Umbilical Vein Endothelial Cells) and freshly isolated human monocytes, we developed an in vitro proatherogenic model with oxidized LDL embedded in very thin (30-50 μm) subendothelial collagen gels, which resembled the accumulation of oxidized LDL in subendothelium of atherosclerotic plaques in vivo, and enabled to trace 3D-kinetics of individual living monocytes. Using this model, we showed that significantly greater number of adherent monocytes crawled on endothelium to paracellular junctions, and started invasion in the presence of oxidized LDL, but once they started invasion, number and kinetics (migration distance, speed, etc. during and after invasion) of monocytes were not significantly different in the presence or absence of oxidized LDL. These results give the first direct evidence that oxidized LDL specifically promotes monocyte post-adhesion dynamics on endothelium (probably crawling), but not invasion itself at junctions, or subendothelial migration after invasion. [Jpn J Physiol 55 Suppl:S93 (2005)]