Cerivastatin Suppresses Lipopolysaccharide-Induced ICAM-1 Expression through Inhibition of Rho GTPase in BAEC

Abstract

We investigated the effect of cerivastatin on lipopolysaccharide (LPS)-induced intercellular adhesion molecule-1 (ICAM-1) expression in bovine aortic endothelial cells. Cerivastatin suppressed LPS-induced ICAM-1 mRNA expression. Cotreatment with geranylgeranylpyrophosphate reversed the effect of cerivastatin. Because Rho undergoes geranylgeranyl modification, we elucidated whether Rho is involved in LPS-induced ICAM-1 expression. Inhibition of Rho activity by Clostridium botulinum C3 transferase or by overexpression of RhoA T19N, a dominant-negative mutant of RhoA, decreased LPS-induced ICAM-1 expression. Although cerivastatin up-regulated endothelial nitric oxide synthase (eNOS), inhibition of nitric oxide (NO) synthesis by cotreatment with Nω-nitro-l-arginine methyl ester (L-NAME) exhibited no influence on the effect of cerivastatin. The present results indicate that cerivastatin prevents LPS-induced ICAM-1 expression in endothelial cells via inhibition of Rho activity. This inhibitory effect is likely unrelated to up-regulation of eNOS.