title: Lacidipine inhibits the activation of the transcription factor NF-kappaB and the expression of adhesion molecules induced by pro-oxidant signals on endothelial cells.
abstract: OBJECTIVE
  The adhesion of monocytes to endothelium, an early event in atherosclerosis is mediated by cell adhesion molecules. Signal-transduction pathways for these binding molecules include the translocation of the transcription factor NF-kappaB; moreover, intracellularly generated oxygen-derived free radicals play a major role in this process. In this study we evaluated the extent to which lacidipine, a calcium antagonist with antioxidant properties, affects the expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin on human umbilical vein endothelial cells, induced by different pro-oxidant signals such as oxidized low density lipoprotein (LDL) and tumor necrosis factor-alpha (TNF-alpha).
  
  
  METHODS
  We incubated 5 micromol/l Cu2+-oxidized LDL and TNF-alpha (2 ng/ml) with human umbilical vein endothelial cells for 48 and 6 h, respectively. ICAM-1, VCAM-1 and E-selectin were measured by flow cytometry. NF-kappaB was evaluated by electrophoretic mobility shift assay.
  
  
  RESULTS
  The incubation of 5 micromol/l Cu2+-oxidized LDL not only caused a dose-dependent increase in ICAM-1, VCAM-1 and E-selectin (P < 0.001), but also synergically increased their TNF-alpha-induced expression (P < 0.001). The addition of lacidipine to human umbilical vein endothelial cells significantly reduced the expression of ICAM-1, VCAM-1 and E-selectin induced by TNF-alpha alone or with oxidized LDL (P < 0.001). The reduction in adhesion molecule expression caused by lacidipine was paralleled by a significant fall in NF-kappaB translocation.
  
  
  CONCLUSIONS
  The results suggest that lacidipine may have prevented NF-kappaB-mediated adhesion molecule expression by exerting its effects on oxygen-derived free radicals. The results support previous observations that lacidipine may have therapeutic effects in atherosclerosis.
authors.affiliation: Istituto di Semeiotica e Nefrologia Medica, Università di Verona, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cominacini
authors.forename: U
authors.initials: U
authors.lastname: Garbin
authors.forename: A
authors.initials: A
authors.lastname: Fratta Pasini
authors.forename: T
authors.initials: T
authors.lastname: Paulon
authors.forename: A
authors.initials: A
authors.lastname: Davoli
authors.forename: M
authors.initials: M
authors.lastname: Campagnola
authors.forename: E
authors.initials: E
authors.lastname: Marchi
authors.forename: A M
authors.initials: AM
authors.lastname: Pastorino
authors.forename: G
authors.initials: G
authors.lastname: Gaviraghi
authors.forename: V
authors.initials: V
authors.lastname: Lo Cascio
mesh_terms: D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D002121:Calcium Channel Blockers; D015815:Cell Adhesion Molecules; D004095:Dihydropyridines; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; C060285:lacidipine