Gamma-Linolenic and Pinolenic Acids Exert Anti-Inflammatory Effects in Cultured Human Endothelial Cells Through Their Elongation Products

Mol Nutr Food Res. 2020 Oct;64(20):e2000382. doi: 10.1002/mnfr.202000382. Epub 2020 Sep 16.

Abstract

Scope: Omega-3 fatty acids (FAs) from oily fish reduce cardiovascular disease. This may be partly due to modulation of endothelial cell (EC) inflammation. Fish stocks are declining and there is a need for sustainable alternative FAs. Gamma-linolenic acid (GLA) and pinolenic acid (PLA) are plant-derived FAs, which can fulfil this role.

Methods and results: EA.hy926 cells are exposed GLA and PLA prior to stimulation with tumor necrosis factor (TNF)-α. GLA and PLA are incorporated into ECs, resulting in increases in long-chain derivatives produced by elongase 5, dihomo-gamma-linolenic acid (DGLA), and eicosatrienoic acid (ETA). Both GLA and PLA (50 µm) decrease production of soluble intercellular adhesion molecule-1 (sICAM-1), monocyte chemoattractant protein 1 (MCP-1), and regulated on activation, normal T cell expressed and secreted (RANTES). However, decreases in these mediators are not seen after pre-treatment with GLA or PLA in elongase 5 silenced EA.hy926 cells. DGLA and ETA (10 µm) decrease EC production of sICAM-1, MCP-1, RANTES, and IL-6. All FAs reduce adhesion of THP-1 monocytes to EA.hy926 cells. Both PLA (50 µm) and ETA (10 µm) decrease NFκBp65 phosphorylation.

Conclusion: These effects suggest potential for GLA, PLA and their long-chain derivatives, DGLA and ETA, as sustainable anti-inflammatory alternatives to fish-derived FAs.

Keywords: endothelial cells; gamma-linolenic acid; inflammation; pinolenic acid; polyunsaturated fatty acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8,11,14-Eicosatrienoic Acid / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Fatty Acid Elongases / genetics
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation Mediators / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Linolenic Acids / pharmacokinetics
  • Linolenic Acids / pharmacology*
  • THP-1 Cells
  • Transcription Factor RelA / metabolism
  • gamma-Linolenic Acid / pharmacokinetics
  • gamma-Linolenic Acid / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • ELOVL5 protein, human
  • ICAM1 protein, human
  • Inflammation Mediators
  • Linolenic Acids
  • Transcription Factor RelA
  • Intercellular Adhesion Molecule-1
  • 5,9,12-octadecatrienoic acid
  • gamma-Linolenic Acid
  • Fatty Acid Elongases
  • 8,11,14-Eicosatrienoic Acid