HMG CoA reductase inhibition modulates VEGF-induced endothelial cell hyperpermeability by preventing RhoA activation and myosin regulatory light chain phosphorylation

SPECIFIC AIMSThe beneficial effects of statins are usually assumed to stem from their ability to reduce cholesterol biosynthesis. However, accumulating evidence suggests that statins may also modulate several signaling pathways through their pleiotropic effects. The major aims of this study were to 1) investigate the modulatory effects of statins on VEGF signaling, and 2) characterize the signaling cascade that leads to VEGF-induced glomerular endothelial cell (GEnC) hyperpermeability.PRINCIPAL FINDINGS1. Effect of simvastatin on VEGF-induced permeabilityTo assess the role of simvastatin on VEGF-induced hyperpermeability, we measured transendothelial electrical resistance (TEER) across GEnCs. GEnCs were grown until post-confluent on Transwell® filters, exposed to various concentrations of VEGF (25, 50, and 100 ng/mL), and the electrical resistance of the filter was subsequently measured using a Millicell-Electrical Resistance System. After 30 min of exposure to various concentrations of VEGF, GEnCs displa...