Human gene array analysis of THP-1 macrophages exposed to lipoprotein hydrolysis products generated by lipoprotein lipase

Macrophage lipoprotein lipase (LPL) contributes to atherogenesis. However, the complete effect of LPL hydrolysis products and its free fatty acid (FFA) component on modifying genes associated with macrophage-derived foam cell formation are not fully understood. I hypothesized that the FFA liberated from lipoproteins by LPL affects the gene expression in macrophages to potentially promote atherogenesis. Human microarray analyses on the RNA isolated from THP-1 macrophages treated with lipoprotein hydrolysis products generated by LPL revealed that selected genes associated with ribosome biogenesis, cell cycling, stress response, type I interferon signaling, and lipid accumulation were affected (at false discovery rate ≤ 0.03, n=3). Testing the effects of either the total FFA component of the hydrolysis products, or individual classes of the FFA component, revealed mixed effects on the gene expression profiles. Overall, LPL hydrolysis products appear to affect gene expression profiles that favor foam cell formation, but it is likely that components other than the FFA differentially affect macrophage gene expression