Modulation of phenotypic expression of monocyte subtypes and chemokine receptors in acute myocardial infarction by statins

Abstract

Atherosclerosis is a progressive disease, characterized by lipid and fibrotic element deposition in large caliber arteries. Conditions related to the development of atherosclerosis, as dyslipidemia, hypertension, diabetes and smoking are associated to endothelial dysfunction. There is frequent recurrence of cardiovascular outcomes after acute myocardial infarction and, at this sense, cycles of mobilization of monocyte subtypes (classical, intermediate and nonclassical) secondary to myocardial infarction may determine the colonization of atherosclerotic plaques in different stages of the development, contributing to early recurrence of ischemic events. The recruitment of different monocyte subsets during inflammatory process requires the expression of chemokine receptors CCR2, CCR5 and CX3CR1, to promote the migration of monocytes to the inflammatory site. This project aims to better understand the mechanisms related to the recovery of the ischemic myocardium and coronary disease progression. Specifically, we will study the monocyte subtypes (identification, quantification and phenotypic characterization) related to the early and late evolution of patients with acute myocardial infarction. In addition, the project will involve the expression of the chemokine receptors CCR2, CCR5 and CX3CR1, which have a role in the development of the atherosclerotic plaque. Pharmacological therapeutic strategies will be evaluated since the acute phase of myocardial infarction up to six months of clinical evolution. The better understanding of the differential role of monocyte subsets in the development of coronary disease may be a new strategic target for the comprehension and therapy of acute myocardial infarction. (AU)