Lacidipine inhibits the activation of the transcription factor NF-kappa B and the expression of adhesion molecules induced by pro-oxidant signals on endothelial cells
| Autor: | Luciano Cominacini, T. Paulon, A. Fratta Pasini, E. Marchi, Ulisse Garbin, G. Gaviraghi, Anna Davoli, V. Lo Cascio, M. Campagnola, A. M. Pastorino |
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| Rok vydání: | 1997 |
| Předmět: |
Dihydropyridines
Umbilical Veins Endothelium Physiology Intercellular Adhesion Molecule-1 Biology Umbilical vein Internal Medicine medicine Humans Cell adhesion Cells Cultured Dose-Response Relationship Drug Tumor Necrosis Factor-alpha Cell adhesion molecule NF-kappa B Adhesion Calcium Channel Blockers Molecular biology Lipoproteins LDL Endothelial stem cell medicine.anatomical_structure Lacidipine Biochemistry Electrophoresis Polyacrylamide Gel Endothelium Vascular Cardiology and Cardiovascular Medicine Cell Adhesion Molecules Oxidation-Reduction medicine.drug |
| Zdroj: | Journal of Hypertension. 15:1633-1640 |
| ISSN: | 0263-6352 |
| Popis: | 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-κB; 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-α (TNF-α). Methods We incubated 5 μmol/l Cu 2+ -oxidized LDL and TNF-α (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-KB was evaluated by electrophoretic mobility shift assay. Results The incubation of 5 μmol/l Cu 2+ -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-α-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-α 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-KB translocation. Conclusions The results suggest that lacidipine may have prevented NF-κB-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. |
| Databáze: | OpenAIRE |
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