Ezetimibe inhibe la adhesión y la migración de monocitos a través de la ruta de las proteincinasas activadas extracelularmente (p44/p42ERK1/2

Resum

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/p42ERK1/2, 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/p42ERK1/2 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/p42ERK1/2 (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/p42ERK1/2 MAPK signalling pathway seems to play a role in this anti-inflammatory effect.