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- W2078113480 abstract "Abstract Statins exert beneficial effects on the cardiovascular system independently of their lipid lowering properties. We recently developed in vitro models that mimic hemodynamic conditions encountered in vivo at sites of atherosclerotic predilection (arterial bifurcation). We hypothesize that the statins will inhibit pre-atherosclerotic activation of endothelial cell adhesion molecules induced by forces such as disturbed flow or elevated pressure. We investigated the effects of simvastatin on cytokine induced upregulation of endothelial cell adhesion molecules, such as VCAM-1 (vascular cell adhesion molecule), ICAM-1 (intracellular adhesion molecule) and E-Selectin. Human microvascular endothelial cells, cultured in a collagen coated 96 well plates, were activated with an inflammatory cytokine, TNF-α for 6 hours. The expression of cell adhesion molecules was investigated with or without pre-treatment with simvastatin. The expression of CAMs was evaluated by enzyme linked immunocellular assay (ELICA), and independently by flow cytometry. TNF-α increased cell adhesion molecule expression in a dose dependent fashion. Stimulation of the cells with TNF-α (in concentrations ranging from 1–100 ng/ml) for 6 h resulted in up to a 4 fold upregulation of VCAM-1 expression, 16 and 6 fold upregulation of ICAM-1 and E-selectin. With 10 μM simvastatin, similar cytokine induction was attenuated, for example VCAM by up to 35%. We conclude that simvastatin efficiently mitigated cytokine-induced activation of the atherosclerotic endothelial phenotype, as evidenced by the downregulation of CAMs. Current experiments are investigating the effects of simvastatin on flow induced CAM expression. We propose that simvastatin may interfere with key signaling events involved in endothelial cell activation by inflammatory mediators such as those that may be encountered during surgical procedures." @default.
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- W2078113480 date "2003-10-01" @default.
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- W2078113480 title "Simvastatin mitigates cytokine induced cell adhesion molecule upregulation in cultured human endothelial cells" @default.
- W2078113480 doi "https://doi.org/10.1016/j.jss.2003.08.044" @default.
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