Lowering the n-6/n-3 PUFAs ratio inhibits the formation of THP-1 macrophage-derived foam cell

Abstract

BackgroundThe balance between n-6 and n-3 PUFAs is an important determinant in the risk for cardiovascular disease. The study was to investigate the influence of the n-6 and n-3 PUFAs ratio on the formation of THP-1 monocyte-derived foam cells and explore the probable mechanism of anti-atherosclerosis.MethodsTHP-1 monocyte cells were cultured with PMA and ox-LDL to establish a foam-cell model, while treated with different ratios of n-6 to n-3 PUFAs for 48 h. The cholesterol of foam cells was measured by a cholesterol assay kit. The levels of IL-6 and TNFα in supernatant were detected with ELISA methods. The expressions of CD36, ABCA1, ACAT1, PPARγ and LXRα mRNA were detected with real-time PCR.ResultsCompared with the foam cell model group, the low and middle ratio of n-6 to n-3 PUFAs groups decreased the intracellular concentration of cholesterol (P < 0.01), but the high n-6/n-3 PUFAs ratio did not. Fatty acids decreased the level of IL-6 and TNFα in supernatant in a ratio-dependent manner. Fatty acids treatment also decreased the expressions of CD36、ACTA1、PPARγ、LXRα mRNA in a ratio-dependent manner.ConclusionsLowering the ratios of n-6 to n-3 PUFAs can decrease the secretion of inflammatory cytokines then reduce the expressions of CD36 and ACAT1 mRNA. As well, it can decrease the expressions of CD36 mRNA through the PPARγ pathway. This leads to less cholesterol ingestion into the cells and decreased synthesis of cholesteryl ester, which inhibits the formation of the foam cells, further preventing the occurrence and development of atherosclerosis.