Investigation of the potential anti‐inflammatory properties of Simvastatin
Kirstie Alison Eccles, Shervanthi Homer‐Vanniasinkam, Karen E. Porter, Anne Margaret Graham · The FASEB Journal · 2007
The endothelial cell (EC) adhesion molecule P‐selectin plays a crucial role in early stages of leukocyte recruitment during inflammation. This study investigated effects of simvastatin pre‐treatment on human saphenous vein EC (HSVEC) in an in vitro flow model of inflammation. HSVEC were seeded into 35mm dishes (2×105 cells/ml) and incubated overnight at 37°C. Confluent EC were treated with histamine (5×10–4M;18min). Neutrophils were perfused over HSVEC (1×106 cells/ml) in a glycotech flow chamber (1.1dyne cm2). EC: neutrophil interactions were recorded and counted. Histamine stimulation resulted in significant (p<0.001) increases in tethering from an average of 40 interactions (negative control) to 380 following histamine stimulation. The effects of histamine were significantly (p<0.001) reduced to levels comparable to the negative control by pre‐treatment of the HSVEC with simvastatin (1μM;6h). Statin effects on histamine stimulated EC were reversed by mevalonate, mean tethering interactions not significantly different from histamine treated EC. These results show the anti‐inflammatory effects of simvastatin to be dependent on a reduction in endothelial P‐selectin expression in an HMG‐CoA reductase dependent manner. Funded by Heart Research UK.