Docosahexaenoic acid and eicosapentaenoic acid suppress adhesion molecule expression in human aortic endothelial cells via differential mechanisms

Chun-Ying Huang, Wayne Huey-Herng Sheu, An-Na Chiang
Molecular Nutrition & Food Research 2015, 59 (4): 751-62

SCOPE: Dietary PUFAs modulate the progression of cardiovascular disease, but the underlying mechanisms within vascular cells remain unclear. The aim of this study was to investigate the biological function and regulatory mechanisms of PUFAs in LPS-activated human aortic endothelial cells (HAECs).

METHODS AND RESULTS: To simulate the in vivo conditions of atherosclerosis, we have established an in vitro model in which THP-1 monocytes adhere to HAECs. Our results showed that n-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) remarkably attenuated the adhesion of THP-1 cells to HAECs, probably through inhibiting the expression of VCAM-1 and ICAM-1. Using lipid raft isolation and confocal microscopy, we found that DHA and EPA suppressed the translocation of TLR4 into lipid rafts. Furthermore, DHA and EPA inhibited the ubiquitination and translocation of TRAF6, and the phosphorylation of TAK1, p38, and IκBα. We demonstrated that DHA reduced the phosphorylation of PKR, but EPA increased the expression of A20. Additionally, silencing of A20 reversed the inhibitory effect of EPA on the expression of adhesion molecules.

CONCLUSION: Our study revealed differential signaling pathways modulated by n-3 PUFAs in LPS-stimulated HAECs. These signaling pathways are potential targets for the prevention of atherosclerotic progression.

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