Narmadaa Thyagarajan - Mar 4

Analysis of differentially regulated gene expression in human macrophages exposed to LPL-hydrolyzed lipoprotein products

Lipoprotein lipase (LPL) is a member of the sn-1 lipase subfamily that plays a crucial role in hydrolyzing triglyceride-rich lipoproteins, such as very low-density lipoproteins and chylomicrons. Several lines of evidence suggest that LPL expressed by macrophages in the atherosclerotic plaque may promote atherosclerosis. However, the mechanism by which macrophage LPL causes foam cell formation is poorly understood. Thus, we hypothesized that the lipid hydrolysis products generated from total lipoprotein hydrolysis by LPL will alter gene expression in human macrophages, leading them to transform into foam cells. To test our hypothesis, we treated macrophages cells with LPL hydrolysis products and we assessed the expression of transcripts using microarray. Our array data show that the expression of 317 genes was differentially regulated in our LPL hydrolysis product treatment at a false discovery rate (FDR) < 0.03. We performed gene ontology studies and selected 7 important biological processes that were significantly over-represented at FDR < 0.03. Our data suggest that LPL hydrolysis products may modulate ribosomal biogenesis, cell cycle, and induce stress response in macrophages cells. Interestingly, we found 63 small nucleolar RNAs that were significantly up-regulated at FDR < 0.03. To confirm some of the array data, we validated the expression of select genes using qPCR. Taken together, our study provides new insights in understanding the role of LPL hydrolysis products in foam cell formation.

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