Effect of simvastatin on LPS-induced EC permeability and cytoskeletal rearrangement. A: compared with untreated controls, EC monolayer permeability is significantly increased in response to LPS (1 μg/ml, 1.5 h) as measured by FITC-dextran translocation (*P < 0.05). Independently, simvastatin pretreatment (5 μM, 16 h) and Rho kinase inhibition (Y-27632, 10 mM, 30 min) both significantly attenuated LPS-induced (1 μg/ml, 1.5 h) EC barrier disruption (**P < 0.05 and †P < 0.05) (n = 3 for each condition). EC barrier protection by simvastatin was abrogated by concomitant treatment with geranylgeranyl pyrophosphate (GGPP; 10 μM, 16 h). B: EC monolayer protection by simvastatin corresponds to early evidence of decreased LPS-induced (1 μg/ml, 1.5 h) paracellular gaps by immunofluorescence (white arrows) in simvastatin-treated EC (5 μM, 16 h).