title: Alpha-tocopherol and BAY 11-7082 reduce vascular cell adhesion molecule in human aortic endothelial cells.
abstract: BACKGROUND
  In endothelial dysfunction, vascular cell adhesion molecule-1 (VCAM-1), E-selectin and intercellular adhesion molecule-1 (ICAM-1) expression (collectively termed cell adhesion molecules; CAMs) increase at sites of atherosclerosis and are stimulated by proinflammatory cytokines such as tumor necrosis factor-α (TNF-α).
  
  
  METHODS
  We evaluated the effect of alpha-tocopherol (AT; 10-150 µM) and BAY 11-7082 (BAY; 0.1 or 1 µM) on CAMs mRNA expression as well as their protein in soluble release form (sCAMs) in human aortic endothelial cells (HAECs) activated by TNF-α (1 or 10 ng/ml). Also, we determined the extent of lymphocyte adhesion to activated HAECs.
  
  
  RESULTS
  BAY reduced VCAM-1, E-selectin and ICAM-1 mRNA expression by 30, 30 and 10%, respectively. Furthermore, protein reduction of sVCAM-1 by 70%, sE-selectin by 51% and sICAM-1 by 25% compared to HAECs stimulated by TNF-α was observed (p < 0.05). AT (50, 75 and 150 µM) decreased VCAM-1 mRNA expression by 30% and sVCAM-1 protein by 33% compared to HAECs stimulated by TNF-α (p < 0.05). TNF-α-activated HAEC adhesion to human Jurkat T lymphocytes was higher compared to nonactivated HAECs (p < 0.05). BAY (2 and 5 µM) reduced this lymphocyte adhesion (p < 0.05).
  
  
  CONCLUSIONS
  BAY reduces all the CAMs studied as well as cell adhesion, while AT selectively inhibits VCAM-1; both induce endothelial dysfunction improvement.
authors.affiliation: Unitat de Recerca en Lípids i Arteriosclerosi, CIBERDEM, Hospital Universitari Sant Joan, IISPV, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Ursula
authors.initials: U
authors.lastname: Catalán
authors.forename: Sara
authors.initials: S
authors.lastname: Fernández-Castillejo
authors.forename: Laia
authors.initials: L
authors.lastname: Pons
authors.forename: Mercedes
authors.initials: M
authors.lastname: Heras
authors.forename: Gemma
authors.initials: G
authors.lastname: Aragonés
authors.forename: Neus
authors.initials: N
authors.lastname: Anglès
authors.forename: Jose-Ramon
authors.initials: JR
authors.lastname: Morelló
authors.forename: Rosa
authors.initials: R
authors.lastname: Solà
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D019169:Jurkat Cells; D009570:Nitriles / Q000494:pharmacology*; D012333:RNA, Messenger; D013450:Sulfones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D019040:E-Selectin; D009570:Nitriles; D012333:RNA, Messenger; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D024502:alpha-Tocopherol