Simvastatin reduces VCAM-1 expression in human umbilical vein endothelial cells exposed to lipopolysaccharide.

ABSTRACT

OBJECTIVE: Reducing the expression of endothelial cell adhesion molecules (ECAMs) is known to decrease inflammation-induced vascular complications. In this paper we looked at whether statins can reduce inflammation-induced ECAM expression after lipopolysaccharide (LPS) treatment in endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were pretreated with different concentrations of simvastatin, atorvastatin, and rosuvastatin and subsequently exposed to 5 µg/ml LPS. Semi-quantitative RT-PCR analysis was used to measure the mRNA expression of ECAMs, including VCAM-1, ICAM-1, and E-selectin. RESULTS: VCAM-1 mRNA appeared to be the only target that was affected by the statins, with its expression being partially and almost completely reduced by simvastatin at 50 and 125 µM concentrations, respectively, and only partially reduced by atorvastatin, but not reduced by rosuvastatin. VCAM-1 protein production was inhibited by simvastatin at concentrations from 5 to 125 µM. Leukocyte-endothelial cell adhesion assay revealed that simvastatin could inhibit the adhesion of labelled U937 cells to the HUVEC monolayer. CONCLUSIONS: This study showed that simvastatin reduces VCAM-1 expression in HUVECs exposed to LPS and decreases leukocyte-endothelial cell adhesion.