Changes to small RNA expression in macrophages in response to very low-density lipoprotein lipid hydrolysis by lipoprotein lipase and NADPH oxidase inhibition.

objectiveWe previously reported that hydrolysis products (HP) generated from total lipoproteins via lipoprotein lipase (LPL) significantly changed the transcriptome of human macrophages, including an increased representation of small nucleolar RNAs, but we did not extensively examine small-coding RNAs in general. The expression of small nucleolar RNAs was previously reported to increase in cardiomyocytes through an increase of reactive oxygen species (ROS) generation by NADPH oxidase (NOX). Thus, we hypothesized that the HP induced ROS production in macrophages through NOX activity, resulting in changes to small RNA transcripts.

resultsWe examined whether very low-density lipoprotein HP could induce ROS production via NOX within the THP-1 human macrophage model. We showed that ROS production was indeed increased, and it was in-part due to NOX. We further examined changes to small RNA expression using RNA-seq in the absence or presence of HP, and whether those changes could be reversed by NOX inhibition. We identified eight differentially expressed small RNAs: three with differed expression in response to HP, and five with differed expression in response to NOX inhibition in the presence of HP. We conclude that LPL drives ROS production in macrophages via NOX to subsequently influence small RNA expression profiles.