HMG-CoA reductase inhibitors reduce adhesion of human monocytes to endothelial cells.
HMG-CoA reductase inhibitors (statins) are believed to reduce coronary heart disease by mechanisms in addition to their well-known cholesterol-lowering effect. We studied the effect of these drugs on monocyte cell adhesion to endothelium. Pretreatment of monocytic cells (U937, THP-1, human CD14(+) monocytes) with 0.01-10 microM concentrations of atorvastatin, cerivastatin, or simvastatin significantly reduced cell adhesion to endothelium. In contrast, pretreatment of endothelium with statins did not affect adhesion of monocytes. Adhesion of monocytes to vascular cell adhesion molecule-1-coated dishes was reduced by these drugs. Cerivastatin also reduced PMA induction of NF-kappaB. Since monocyte adhesion to endothelium is an early event in atherogenesis, treatment with statins in prevention of coronary heart disease may have additional salutary effects to lowering of plasma LDL cholesterol. Our results indicate that the reduction of monocyte adhesion by HMG-CoA reductase inhibitors may be considered as a class effect.
Teupser
D
D
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Leipzig, Germany.
Bruegel
M
M
Stein
O
O
Stein
Y
Y
Thiery
J
J
D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics; D019821:Simvastatin / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018950:Lipopolysaccharide Receptors; D016328:NF-kappa B; D011725:Pyridines; D011758:Pyrroles; D012333:RNA, Messenger; D011973:Receptors, LDL; D019010:Vascular Cell Adhesion Molecule-1; D000069059:Atorvastatin; D019821:Simvastatin; C086276:cerivastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D013755:Tetradecanoylphorbol Acetate