AI Article Synopsis

  • Macrophage lipoprotein lipase (LPL) contributes to fat buildup and atherosclerosis, but the specific effects of LPL's breakdown products on foam cell formation are unclear.
  • A study using microarray analyses found that LPL hydrolysis products significantly altered the expression of many genes related to cell functions, stress responses, and lipid metabolism in human THP-1 macrophages.
  • Results showed that the free fatty acids alone did not replicate the same gene regulation effects as the hydrolysis products, indicating that the impact on gene expression is dependent on the unique combinations of lipid species rather than just free fatty acids.

Article Abstract

Macrophage 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 of SNORA56, as well as the expression of genes associated with the cell cycle (PCNA and DKC1 variant 3), stress response (ATF3), type I interferon signaling (IFITM1), and lipid metabolism (CD36 and PLIN2) 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 regulation by the FFA component did not mimic that of the hydrolysis products, suggesting that the regulation of gene expression in THP-1 macrophages depends on the specific combination and concentration of lipid species present in the hydrolysis products, and not solely on FFA.

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Source
http://dx.doi.org/10.1007/s11745-017-4238-1DOI Listing

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