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Transcriptomic Analysis of THP-1 Macrophages Exposed to Lipoprotein Hydrolysis Products Generated by Lipoprotein Lipase.
- Source :
-
Lipids [Lipids] 2017 Mar; Vol. 52 (3), pp. 189-205. Date of Electronic Publication: 2017 Feb 15. - Publication Year :
- 2017
-
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.
- Subjects :
- Cell Cycle Proteins genetics
Cell Line
Cholesterol pharmacology
Fatty Acids, Nonesterified pharmacology
Foam Cells drug effects
Foam Cells metabolism
Gene Expression Regulation drug effects
Humans
Hydrolysis
Lipid Metabolism
Lipoproteins pharmacology
Macrophages metabolism
RNA, Small Nucleolar genetics
Signal Transduction
Triglycerides pharmacology
Gene Expression Profiling methods
Lipoprotein Lipase metabolism
Lipoproteins chemistry
Macrophages drug effects
Oligonucleotide Array Sequence Analysis methods
Subjects
Details
- Language :
- English
- ISSN :
- 1558-9307
- Volume :
- 52
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Lipids
- Publication Type :
- Academic Journal
- Accession number :
- 28205069
- Full Text :
- https://doi.org/10.1007/s11745-017-4238-1