Simvastatin and atorvastatin attenuate VCAM-1 and uPAR expression on human endothelial cells and platelet surface expression of CD40 ligand.
BACKGROUND
In addition to their cholesterol lowering ability, statins have proven pleiotropic effects in the cardiovascular system. Chronic inflammation with interactions between platelets and endothelial cells leads to an upregulation of activity markers of atherosclerosis. The purpose of this study was to investigate the effects of simvastatin and atorvastatin on platelets and endothelial cells in an in vitro endothelial cell model.


RESULTS
After a 24 h incubation period with either simvastatin or atorvastatin (1 μmol/L), human umbilical vein endothelial cells were stimulated for 1 h with lipopolysaccharide (LPS), and were then incubated in direct contact with activated platelets. Platelet surface expression of CD40L and CD62P and expression of ICAM-1, VCAM-1, uPAR and MT1-MMP on endothelial cells were measured by flow cytometry. Supernatants were analyzed by ELISA for soluble MMP-1. The increased expression of VCAM-1 and uPAR on endothelial cells by stimulation with LPS and by direct contact with activated platelets was significantly reduced to a similar extent through pre-incubation with both atorvastatin and simvastatin (p < 0.05). Platelets without endothelial cell contact, but in direct contact with either statin, showed similar significant reductions in surface expression of CD40L (p < 0.005).


CONCLUSIONS
These effects may explain the ability of statins to reduce the progression of atherosclerosis in addition to their cholesterol-lowering properties.
1st Department of Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Germany.
Ksenija
K
Stach
Xuan Duc
XD
Nguyen
Siegfried
S
Lang
Elif
E
Elmas
Christel
C
Weiss
Martin
M
Borggrefe
Joachim
J
Fischer
Thorsten
T
Kälsch
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006538:Heptanoic Acids / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008070:Lipopolysaccharides; D019007:P-Selectin; C524898:PLAUR protein, human; D011758:Pyrroles; D055293:Receptors, Urokinase Plasminogen Activator; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand; D000069059:Atorvastatin; D019821:Simvastatin; D013917:Thrombin; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14