Synergistic effect of scavenger receptor A and low-density lipoprotein receptor on macrophage foam cell formation under inflammatory stress

Abstract

To provide experimental evidence for the effect of inflammation on cholesterol accumulation in macrophages, we investigated the expression of low-density lipoprotein receptor (LDL-R) and scavenger receptor A (SR-A) genes and proteins in the lipopolysaccharide (LPS)-stimulated macrophage-like RAW264.7 cell line. RAW264.7 cells were incubated in serum-free medium in the absence or presence of LDL alone, LDL+LPS and LPS alone. Intracellular cholesterol content, tumor necrosis factor α levels in the supernatants, mRNA and protein expression of LDL-R and SR-A in the treated cells were assessed by Oil Red O staining cholesterol enzymatic assay, enzyme-linked immunosorbent assay, semi-quantitative polymerase chain reaction and western blot analysis, respectively. Our results demonstrated that LPS was able to upregulate SR-A mRNA and protein expression, override LDL-R suppression induced by a high dose of LDL and increase LDL uptake by enhancing receptor expression, leading to foam cell formation in RAW264.7 cells. These findings suggest that the synergy of the upregulation of SR-A and dysregulation of LDL-R under inflammatory stress may contribute to macrophage-derived foam cell formation.