Lacidipine inhibits the activation of the transcription factor NF-kappaB and the expression of adhesion molecules induced by pro-oxidant signals on endothelial cells

J Hypertens. 1997 Dec;15(12 Pt 2):1633-40. doi: 10.1097/00004872-199715120-00065.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium Channel Blockers / pharmacology*
  • Cell Adhesion Molecules / metabolism*
  • Cells, Cultured
  • Dihydropyridines / pharmacology*
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Humans
  • Lipoproteins, LDL / pharmacology*
  • NF-kappa B / metabolism*
  • Oxidation-Reduction
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Umbilical Veins / cytology


  • Calcium Channel Blockers
  • Cell Adhesion Molecules
  • Dihydropyridines
  • Lipoproteins, LDL
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • oxidized low density lipoprotein
  • lacidipine