title: Docosahexaenoic acid and eicosapentaenoic acid suppress adhesion molecule expression in human aortic endothelial cells via differential mechanisms.
abstract: METHODS
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors: Chun-Ying
authors: CY
authors: Huang
authors: Wayne Huey-Herng
authors: WH
authors: Sheu
authors: An-Na
authors: AN
authors: Chiang
mesh_terms: D001011:Aorta / Q000166:cytology*; D050197:Atherosclerosis / Q000188:drug therapy / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D020672:I-kappa B Proteins; D018799:Intercellular Adhesion Molecule-1; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D051197:Toll-Like Receptor 4; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D019010:Vascular Cell Adhesion Molecule-1; D048051:p38 Mitogen-Activated Protein Kinases; D000099151:MAP Kinase Kinase Kinase 7; C000606204:NFKBIA protein, human; C120635:TAX1BP1 protein, human; C495345:TLR4 protein, human; C076529:TNFAIP3 protein, human
keywords: Adhesion molecules; Endothelial cells; TLR4 translocation; TRAF6 ubiquitination; n-3 PUFAs