Pitavastatin up-regulates eNOS production by suppressing miR-155 expression in lipopolysaccharide-stimulated human umbilical vein endothelial cells.

Abstract

Pitavastatin (Pit) has been proved to efficiently inhibit the onset and progression of atherosclerosis. However, the mechanism by which Pit exerts nonlipid-related effects, such as antiinflammatory actions, is not quite clear. Our study aimed at investigating the effect of Pit on the expression of endothelial NO synthase (eNOS) and miR-155 in LPS-stimulated HUVECs to reveal the antiinflammatory mechanism of pitavastatin. HUVECs were isolated from newborn umbilical cords and used in the experiments at passages 2-5. Cells were treated with LPS (0.05, 0.1, 1μg/L) or LPS (0.1μg/L)+Pit (0.01, 0.1, 1μmol/L), untreated cells were used as control. For LPS+Pit induction, cells were firstly incubated with Pit for 1hour before coincubation with LPS for 24hours. eNOS mRNA and miR-155 were detected by RT-PCR, and Western blotting was used to detect protein expression of eNOS. Treatment of HUVECs with LPS enhanced the expression of miR-155 and reduced the expression of eNOS in mRNA and protein level in a dose-dependent manner as revealed by RT-PCR and Western blotting, respectively. Pitavastatin ameliorated LPS-induced endothelial dysfunction through upregulation of eNOS expression and downregulation of miR-155 expression. Pitavastatin increases eNOS expression and inhibits of LPS-induced miR-155 expression.