title: IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal.
abstract: BACKGROUND
  A high-fat diet accompanied by hypertriglyceridemia increases an individual's risk for development of atherosclerosis. An early event in this process is monocyte recruitment through binding to vascular cell adhesion molecule 1 (VCAM-1) upregulated on inflamed arterial endothelium. Diets high in polyunsaturated fatty acids (PUFAs) may provide athero-protection by ameliorating this effect.
  
  
  OBJECTIVE
  We investigated the acute regulation of VCAM-1 expression in human aortic endothelial cells (HAEC) in response to triglyceride-rich lipoproteins (TGRL) isolated from subjects after consumption of a high-fat meal.
  
  
  RESULTS
  Postprandial TGRL isolated from 38 subjects were categorized as proatherogenic or antiatherogenic according to their capacity to alter the inflammatory response of HAEC. Proatherogenic TGRL increased expression of VCAM-1, intercellular adhesion molecule 1 (ICAM-1), and E-selectin by ≈20% compared with stimulation with tumor necrosis factor-α alone, whereas antiatherogenic TGRL decreased VCAM-1 expression by ≈20% while still upregulating ICAM-1. The relative atherogenicity of TGRL positively correlated with particle density of TG, apolipoprotein (Apo)CIII, ApoE, and cholesterol. Ω3-PUFA mimicked the effect of antiatherogenic TGRL by downregulating VCAM-1 expression. TGRL exerted this differential regulation of VCAM-1 by reciprocally modulating expression and activity of the transcription factor interferon regulatory factor 1 (IRF-1) and expression of microRNA 126 (miR-126). Overexpression or silencing of IRF-1 or miR-126 expression recapitulated the proatherogenic or antiatherogenic regulation of VCAM-1.
  
  
  CONCLUSIONS
  In response to a high-fat meal, TGRL bias the inflammatory response of endothelium via transcriptional and posttranscriptional editing of VCAM-1. Subjects with an anti-inflammatory response to a meal produced TGRL that was enriched in nonesterified fatty acids, decreased IRF-1 expression, increased miR-126 activity, and diminished monocyte arrest.
authors.affiliation: Department of Biomedical Engineering, University of California Davis, Davis, CA 95616, USA.
authors.forename: Chongxiu
authors.initials: C
authors.lastname: Sun
authors.forename: Kenan
authors.initials: K
authors.lastname: Alkhoury
authors.forename: Ying I
authors.initials: YI
authors.lastname: Wang
authors.forename: Greg A
authors.initials: GA
authors.lastname: Foster
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Radecke
authors.forename: Kayan
authors.initials: K
authors.lastname: Tam
authors.forename: Christina M
authors.initials: CM
authors.lastname: Edwards
authors.forename: Marc T
authors.initials: MT
authors.lastname: Facciotti
authors.forename: Ehrin J
authors.initials: EJ
authors.lastname: Armstrong
authors.forename: Anne A
authors.initials: AA
authors.lastname: Knowlton
authors.forename: John W
authors.initials: JW
authors.lastname: Newman
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Passerini
authors.forename: Scott I
authors.initials: SI
authors.lastname: Simon
mesh_terms: D001011:Aorta / Q000166:cytology; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D004041:Dietary Fats / Q000008:administration & dosage*; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics* / Q000378:metabolism*; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019518:Postprandial Period / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1