Abstract

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. 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. 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. 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.

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