
<ArticleTitle><prot>Hmg-CoA reductase</prot> inhibitor modulates monocyte-endothelial cell interaction under physiological flow conditions in vitro: involvement of Rho GTPase-dependent mechanism.</ArticleTitle>
<AbstractText><prot>3-Hydroxy-3-methylglutaryl coenzyme A reductase</prot> inhibitors, or statins, have been reported to exert actions independent of their lipid-lowering effects. To critically assess the effects of statins on monocyte-endothelial cell interactions, we used an in vitro model that mimicked physiological flow conditions. Monocytic U937 cells were incubated in the presence of <prot>cerivastatin</prot> for 48 hours. Adhesive interactions of statin-treated U937 cells were then analyzed by use of activated (interleukin-1beta 10 U/mL, 4 hours) human umbilical vein endothelial cells in an in vitro flow apparatus. Flow cytometric analysis of adhesion molecules and measurement of <prot>F-actin</prot> content in U937 cells were performed before and after statin treatment. Preincubation with <prot>cerivastatin</prot> significantly decreased U937 firm adhesion to activated human umbilical vein endothelial cells, whereas U937 rolling was not decreased. Fluorescence-activated cell sorter analysis revealed downregulation of U937 surface expression of <prot>CD11a</prot>, <prot>CD18</prot>, and <prot>VLA4</prot> after statin treatment. <prot>Cerivastatin</prot> significantly reduced <prot>F-actin</prot> content in U937 cells and inhibited <prot>RhoA</prot> translocation, whereas preincubation with <prot>C3</prot> exoenzyme reduced U937 adhesion under flow. <prot>Cerivastatin</prot> reduces monocyte adhesion to vascular endothelium under physiological flow conditions via downregulation of integrin adhesion molecules and inhibition of <prot>actin</prot> polymerization via <prot>RhoA</prot> inactivation. Our findings have important implications for the lipid-independent effects of statins.</AbstractText>
