Fig. 6. Model summarizing the proposed effects of differences in mTRIB1 expression on foam cell expansion in early-stage atherosclerosis.

Factors up-regulating mTRIB1 expression in human MDMs and plaque macrophages simultaneously increase cholesterol and neutral lipid uptake, with no compensatory rise in cholesterol efflux. Schematic recognizes that increased OLR1 expression increases the probability of this scavenger receptor assembling as a hexamer made up of three homodimers on the macrophage cell surface and that this configuration leads to a marked increase in its affinity for oxLDL (9) and hence OLR1-mediated uptake of oxLDL lipids. In the setting of no compensatory rise in HDL-mediated cholesterol efflux, accelerated foam cell expansion and increased atheroma burden ensue, highlighting the therapeutic potential of inhibiting macrophage Trib1 expression to block the gene expression changes that both promote macrophage cholesterol uptake and cholesteryl ester formation accumulation and prevent the increased hydrolysis of the accumulated cholesteryl ester and thus the up-regulation of the reverse cholesterol transport pathway to mediate the removal of cholesterol from the arterial wall.