Premium
Omega‐3 polyunsaturated fatty acids protect endothelial adhesion of monocytes through FFA4 in monocytes
Author(s) -
Lee SeungJin,
Im DongSoon
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.513.6
Subject(s) - gpr120 , monocyte , polyunsaturated fatty acid , cell adhesion molecule , chemistry , microbiology and biotechnology , cell adhesion , receptor , biology , biochemistry , g protein coupled receptor , fatty acid , immunology , cell
A G protein‐coupled receptor (GPCR) named free fatty acid receptor 4 (FFA4, also known as GPR120) was found to act as a GPCR for omega‐3 polyunsaturated fatty acids (n−3 PUFA). Recently, FFA4 is known to participate in the progression of atherosclerosis, however, the underlying mechanisms are unclear. Thus, this study investigated the molecular mechanisms responsible for monocyte adhesion to the vascular endothelium, which is a key early event in macrophage foam cell formation. In ex vivo study, LPS‐induced the primary monocyte adhesion to the vascular endothelial cells were significantly attenuated by pretreatment of EPA and DHA, a representative n−3 PUFA. This EPA and DHA‐induced inhibition were blunted by primary monocytes isolated from FFA4 (−/−) mice. In in vitro study, The LPS‐induced monocyte adhesion to the endothelial cells and adhesion molecule, Mac‐1 expression were significantly attenuated by pretreatment of EPA and DHA in monocytes. This EPA and DHA‐induced inhibition was blunted by pretreatment of AH7614 (a FFA4 antagonist) and by transfection of FFA4 siRNA, suggesting a pivotal role of FFA4 on LPS‐induced monocyte adhesion to the endothelial cells and Mac‐1 expression. In addition, in promoter activity analysis and chromatin immunoprecipitation assays to identify transcription factors involved in EPA and DHA inhibited LPS‐induced Mac‐1 expression, both AP‐1 and NF‐κB played central roles to increase Mac‐1 transcription in LPS‐treated monocytes. The results of this study suggest that n‐3 PUFA protect monocyte adhesion to vascular endothelial cells and Mac‐1 expression via signaling pathways involving AP‐1 and NF‐κB by activating FFA4 in monocytes, leading to increased foam cell formation in the development of atherosclerosis. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .