Impact of Polyunsaturated Fatty Acids on miRNA Profiles of Monocytes/Macrophages and Endothelial Cells—A Pilot Study

Abstract

Alteration of miRNAs and dietary polyunsaturated fatty acids (PUFAs) underlies vascular inflammation. PUFAs are known to be incorporated into the cell membrane of monocytes/macrophages or endothelial cells, the major cellular players of vascular diseases, thereby affecting cellular signal transduction. Nevertheless, there are no investigations concerning the PUFA impact on miRNA expression by these cells. With regard to the key role miRNAs play for overall cellular functionality, this study aims to elucidate whether PUFAs affect miRNA expression profiles. To this end, the monocyte/macrophage cell line RAW264.7 and the endothelial cell line TIME were enriched with either docosahexaenoic acid (DHA; n3-PUFA) or arachidonic acid (AA; n6-PUFA) until reaching a stable incorporation into the plasma membrane and, at least in part, exposed to an inflammatory milieu. Expressed miRNAs were determined by deep sequencing, and compared to unsupplemented/unstimulated controls. Data gained clearly show that PUFAs in fact modulate miRNA expression of both cell types analyzed regardless the presence/absence of an inflammatory stimulator. Moreover, certain miRNAs already linked to vascular inflammation were found to be affected by cellular PUFA enrichment. Hence, vascular inflammation appears to be influenced by dietary fatty acids, inter alia, via PUFA-mediated modulation of the type and amount of miRNAs synthesized by cells involved in the inflammatory process.

Impact of aerobic exercise and fatty acid supplementation on global and gene-specific DNA methylation

“…While exercise and FA supplementation may directly influence DNMT expression, these interventions may modulate DNMT expression by intermediary mechanisms. The expression of several miRNAs, including miRNA-29 −130 and −148, are associated with: DNMT expression [74][75][76][77], exercise [78] and FA supplementation [79][80][81]. IL-6 protein levels have been reported to regulate DNMT mRNA expression [30][31][32] via the modulation of miRNA [29].…”

The Influence of Diet on MicroRNAs that Impact Cardiovascular Disease

“…Among cardioprotective nutritional components that can affect the expression of miRNAs are omega-3 and omega-6 PUFAs [94]. PUFAs were observed to downregulate miRNA-146a in endothelial cells with lipopolysaccharide-induced inflammation [95]. This miRNA can contribute to the induction of vascular inflammation [96].…”

Quantitative proteomics reveals key proteins regulated by eicosapentaenoic acid in endothelial activation

“…Previous studies have primarily focused on a limited number of receptors and signaling pathways [5,6]. Recently, some systematic studies using metabolomics [9] and RNA sequencing [18] have been performed to explore the global perspective; however, most cellular functions are mediated by proteins, and a proteomic study of the biological mechanism of EPA has been lacking. In our study, the proteomic results were consistent with the Western blotting ( Figs.…”