Eicosapentaenoic Acid (EPA) Modulates Expression of Inflammatory Proteins in Pulmonary Endothelial Cells following Exposure to Air Pollution Particles

Abstract

Lead Author's Financial Disclosures Nothing to disclose. Study Funding Amarin Pharma Inc. and Elucida Research. Background/Synopsis Air pollution contributes to global mortality by causing systemic inflammation and endothelial dysfunction in vascular disease, including atherosclerosis. The omega-3 fatty acid eicosapentaenoic acid (EPA) reduced cardiovascular events in high-risk patients (REDUCE-IT). EPA and omega-3 fatty acids can improve cardiac function and lipid levels in subjects exposed to air pollution particulate matter (PM) but underlying the mechanism is not understood. Objective/Purpose To test the ability of EPA to modulate expression of inflammatory proteins and related pathways in pulmonary endothelial cells following exposure to air pollution PMs of different sizes. Methods Human pulmonary ECs (PECs) were pretreated with EPA (40 micromolar) for 2 h before addition of particulate matter (PMs) with two different diameter ranges for 8 h. The PMs had an average of 5.9 micrometers from collected urban air (urban PMs) and 2.8 micrometers (fine PMs). PMs were delivered to the cells at 50 microgram/mL. Cell extracts from each treatment group were analyzed with LC/MS-based proteomics to measure relative expression levels of proteins. Only significant (p<0.05) changes in expression between treatment groups >1- fold were analyzed using differential enrichment analysis of proteomics data (DEP) and included in gene set enrichment analysis (GSEA). Results EPA significantly modulated expression of 205 and 347 proteins relative to fine and urban PMs, respectively. Among pathways modulated by both PMs was neutrophil degranulation (Gene Ontology ID: 0043312), where fine and urban PMs modulated 36 and 13 proteins, respectively. Common to both PMs were eight proteins, including 1.5-fold and 1.3-fold increases in C-X-C motif chemokine 6 (CXCL6). EPA treatment modulated 22 and 35 proteins associated with neutrophil degranulation compared to fine and urban PMs, respectively. Relative to fine PMs, EPA increased expression of heat shock protein 90-β; and decreased expression of interleukin enhancer-binding factor 2 (ILF2). Compared to urban PMs, EPA decreased expression of CXCL6 and increased expression of glutathione S-transferase P. Conclusions EPA significantly modulated expression of various inflammatory proteins in pulmonary ECs during exposure to multiple air pollution PMs. These findings support a novel vascular benefit for EPA under inflammatory conditions caused by air pollution PMs. Nothing to disclose.