Lovastatin-stimulated superinduction of E-selectin, ICAM-1 and VCAM-1 in TNF-alpha activated human vascular endothelial cells.
Inhibitors of HMG-CoA reductase (statins) reveal important pharmacological effects in addition to reducing the plasma LDL cholesterol level. In the pathogenesis of arteriosclerosis, transendothelial migration of various leukocytes including monocytes is a crucial step. We, therefore, investigated the expression of E-selectin, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in vascular endothelial cells as influenced by lovastatin. Human umbilical vein endothelial cells (HUVECs) express significant amounts of selectins and cell adhesion molecules (CAMs) within a few hours after stimulation with TNF-alpha. This effect is potentiated by 100-200% when the cells are pretreated with 0.1-2.5 microM lovastatin. The lovastatin-mediated increase in the cytoplasm and at the cell surface is dose-dependent and significant at lovastatin concentrations comparable to plasma levels in patients under lovastatin treatment. The lovastatin-potentiated increase of E-selectin and CAMs is correlated with a corresponding increase of selectin- and CAM-specific mRNA. We conclude that, in vivo, statin treatment could trigger an enhanced recruitment of macrophages that might support the cholesteryl ester efflux from the arteriosclerotic plaque.
Schmidt
Annette
A
Institute for Arteriosclerosis Research, University of Münster, Domagkstr. 3, D-48149, Münster, Germany. annschm@uni-muenster.de
Goepfert
Christian
C
Feitsma
Kirsten
K
Buddecke
Eckhart
E
D019040:E-Selectin / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology*; D019087:Selectins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects* / Q000378:metabolism
D019040:E-Selectin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019087:Selectins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D008148:Lovastatin