JACC. Basic to translational science, Volume 10, Issue 3, 30 5 2024, Pages 383-395 EPA Induces an Anti-Inflammatory Transcriptome in T Cells, Implicating a Triglyceride-Independent Pathway in Cardiovascular Risk Reduction. Reilly NA, Dekkers KF, Molenaar J, Arumugam S, Kuipers TB, Ariyurek Y, Hoeksema MA, Jukema JW, Heijmans BT

Twice-daily intake of purified eicosapentaenoic acid (EPA) reduces atherosclerotic cardiovascular disease risk in patients with high triglycerides, but its exact mechanism remains unclear. We exposed non-activated CD4+ T cells to 100μM EPA, oleic acid, palmitic acid, or control, and conducted RNA and ATAC-sequencing after 48 hours. EPA exposure downregulated immune response-related genes like HLA-DRA, CD69, and IL2RA, and upregulated oxidative stress prevention genes like NQO1. Transcription factor footprinting showed decreased GATA3 and PU.1, and increased REV-ERB. These effects were specific to EPA, suggesting it induces an anti-inflammatory transcriptomic landscape in CD4+ T cells, contributing to its observed cardiovascular benefits.

JACC Basic Transl Sci. 2024 10;10(3):383-395