Transcriptomic Analysis of THP-1 Macrophages Exposed to Lipoprotein Hydrolysis Products Generated by Lipoprotein Lipase

AbstractMacrophage lipoprotein lipase (LPL) induces lipid accumulation and promotes atherosclerosis. However, the effects of lipoprotein hydrolysis products generated by LPL on macrophage-derived foam cell formation are not clearly understood. Thus, we analyzed the transcriptomic response to hydrolysis products via microarray analyses on RNA isolated from human THP-1 macrophages incubated with total lipoprotein hydrolysis products generated by LPL. The expression of 183 transcripts was significantly upregulated and 133 transcripts were significantly downregulated. Bioinformatics analyses revealed that there was a significant over-representation of genes involved in cell cycling, stress response, type I interferon signaling, cellular metal ion homeostasis, sterol metabolism, and nuclease activity. Interestingly, transcripts for 63 small nucleolar RNA were significantly upregulated. We verified the microarray data by quantitative real-time PCR and found that the expression ofSNORA56, as well as the expression of genes associated with the cell cycle (PCNA andDKC1 variant 3), stress response (ATF3), type I interferon signaling (IFITM1), and lipid metabolism (CD36 andPLIN2) were significantly affected by LPL hydrolysis products. To determine if the free fatty acid (FFA) component of total lipoprotein hydrolysis products is sufficient to alter the expression of these genes, THP-1 macrophages were also incubated with the total FFA or individual classes of the FFA component. The gene...

Source: Lipids - February 14, 2017 Category: Lipidology Source Type: research