EPA Induces an Anti-Inflammatory Transcriptome in T Cells, Implicating a Triglyceride-Independent Pathway in Cardiovascular Risk Reduction

JACC Basic to Translational Science, vol. 10, pp. 383–395

Abstract

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.

Authors 9

1. Nathalie A. Reilly Aachen

   Leiden University Medical Center

   Affiliation as printed

   Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands

2. Koen F. Dekkers Aachen Molecular Epidemiology Department of Biomedical Data Sciences

   Leiden University Medical Center

   Affiliation as printed

   Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands

3. Jeroen Molenaar Aachen Molecular Epidemiology Department of Biomedical Data Sciences

   Leiden University Medical Center

   Affiliation as printed

   Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands

4. Sinthuja Arumugam Aachen Molecular Epidemiology Department of Biomedical Data Sciences

   Leiden University Medical Center

   Affiliation as printed

   Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands

5. Thomas B. Kuipers Aachen

   Leiden University Medical Center

   Affiliation as printed

   Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands; Sequencing Analysis Support Core, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands

6. Yavuz Ariyürek Aachen Leiden Genome Technology Center Department of Human Genetics

   Leiden University Medical Center

   Affiliation as printed

   Leiden Genome Technology Center, Department of Human Genetics, Leiden University Medical Center, the Netherlands

7. Marten Anne Hoeksema

   Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers · University of Amsterdam

   Affiliation as printed

   Department of Medical Biochemistry, Amsterdam University Medical Center, University of Amsterdam, Amsterdam the Netherlands

8. J. Wouter Jukema Aachen

   Leiden University Medical Center · Netherlands Heart Institute

   Affiliation as printed

   Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands; Netherlands Heart Institute, Utrecht, the Netherlands

9. Bastiaan T. Heijmans corresponding Aachen Molecular Epidemiology Department of Biomedical Data Sciences

   Leiden University Medical Center

   Affiliation as printed

   Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: b.t.heijmans@lumc.nl