EPA Induces an Anti-Inflammatory Transcriptome in T Cells, Implicating a Triglyceride-Independent Pathway in Cardiovascular Risk Reduction
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<sup>+</sup> 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<sup>+</sup> T cells, contributing to its observed cardiovascular benefits.
Authors
- J. Wouter Jukema (ORCID: https://orcid.org/0000-0002-3246-8359)
- Nathalie A. Reilly (ORCID: https://orcid.org/0000-0001-5219-4001)
- Yavuz Ariyürek
- Marten A. Hoeksema (ORCID: https://orcid.org/0000-0001-5981-121X)
- Jeroen Molenaar (ORCID: https://orcid.org/0009-0007-9818-0175)
- Koen F. Dekkers (ORCID: https://orcid.org/0000-0002-4074-7235)
- Bastiaan T. Heijmans (ORCID: https://orcid.org/0000-0001-5918-0534)
- Thomas B. Kuipers (ORCID: https://orcid.org/0000-0001-5373-6765)
- Sinthuja Arumugam
Institutions
- Leiden University Medical Center (NL)
- Netherlands Heart Institute (NL)
- Amsterdam University Medical Centers (NL)
- University of Amsterdam (NL)
Publication Details
- Journal
- JACC Basic to Translational Science
- Published
- 2024-10-31
- DOI
- https://doi.org/10.1016/j.jacbts.2024.09.002
- Citations
- 5
- Primary Topic
- Atherosclerosis and Cardiovascular Diseases
- Type
- article
- Field-Weighted Citation Impact
- 1.20
Funders
- Dutch Cardiovascular Alliance