Toll-like receptor-dependent lipid body formation in macrophage foam cell formation.
OBJECTIVE
The differentiation of macrophages into lipid-laden foam cells is central to the development of atherosclerosis. Traditionally, it has been assumed that the uptake of oxidized low-density lipoprotein by macrophage scavenger receptors is largely responsible for this process. However, in light of recent evidence that these mechanisms may not play as large a role as previously thought, alternative mechanisms of foam cell formation are now being explored.


RESULTS
The stimulation of Toll-like receptor (TLR) signalling by bacterial molecules has been shown to promote the accumulation of lipid in macrophages in the form of intracellular inclusions termed 'lipid bodies'. Interactions between TLR-signalling pathways and the liver-X receptor and peroxisome proliferator-activated receptor-γ signalling pathways modulate the formation of lipid bodies in macrophages and thereby cellular accumulation of cholesterol and triglyceride. These pathways appear to involve TLR-mediated regulation of lipid-binding proteins, cellular cholesterol sensors, lipid-body-associated proteins and secreted autocrine factors, but are independent of scavenger receptor or lipoprotein oxidation-dependent pathways.


CONCLUSIONS
TLR stimulation promotes the accumulation of lipid bodies in macrophages and consequently foam cell formation. The pathways responsible for these processes may constitute novel therapeutic targets for atherosclerosis.
Nicolaou
Giovanna
G
Department of Cardiovascular Sciences, Glenfield General Hospital, University of Leicester, Leicester, UK.
Erridge
Clett
C
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D005487:Foam Cells / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D050356:Lipid Metabolism; D009000:Monocytes / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
D051193:Toll-Like Receptors