• 作者：Paloma Mu&#241 ; oz-Pacheco ; Adriana Ortega-Herná ; ndez ; Arturo Ferná ; ndez-Cruz ; Dulcenombre Gó ; mez-Garre ; ^{mgomezg.hcsc@salud.madrid.org}
• 关键词：Ezetimibe ; Inflamació ; n ; MAP quinasas
• 刊名：Cl¨ªnica e Investigaci¨®n en Arteriosclerosis
• 出版年：2011
• 出版时间：July-August 2011
• 年：2011
• 卷：23
• 期：4
• 页码：160-167
• 全文大小：318 K

lass=""h4"">Introduction

Recently, our group has demonstrated that ezetimibe, a specific inhibitor of intestinal absorption, is able to inhibit vascular inflammation in a rabbit model of atherosclerosis. In this study, we investigated the effect of ezetimibe on the adhesion and migration of human THP-1 monocytes in vitro. We also studied the involvement of the MAP kinase signalling pathway, p44/p42^ERK1/2, as a potential mechanism responsible for the observed effect.

lass=""h4"">Material and methods

Adhesion of THP-1 monocytes was measured as the ability of cells to bind to plates. Migration was studied using two-compartment chambers. The expression of adhesion molecules was assessed by flow cytometry. Activation of p44/p42^ERK1/2 was measured by Western Blot.

lass=""h4"">Results

Preincubation of THP-1 monocytes with ezetimibe prevented PMA-induced adhesion and MCP-1-induced migration in a dose-dependent manner. Preincubation of THP-1 monocytes with ezetimibe also inhibited the expression of the integrins CD11a and CD11b, as well as phosphorylation of p-p44/p42^ERK1/2 (the active form) induced by MCP-1. More than 90 % of cells (evaluated through trypan blue) were viable 1 or 2 days after exposure to ezetimibe.

lass=""h4"">Conclusions

Our results indicate that, in addition to its lipid lowering activity, ezetimibe is able to inhibit the process of adhesion and migration of monocytes in vitro. Blocking of the p44/p42^ERK1/2 MAPK signalling pathway seems to play a role in this anti-inflammatory effect.