Effects of oxidized LDL in macrophages M2: implications in atherosclerosis

• Grant number: 14/20328-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2015
• End date: December 31, 2016
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Jorge Elias Kalil Filho
• Grantee: Fernanda Magalhães Gonçalves
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Atherosclerosis is a chronic disease in which two striking features are observed: retention of lipids and inflammation. Understanding the interaction between immune cells and lipoproteins involved in atherogenesis are urgent challenges, since cardiovascular diseases are the leading cause of death worldwide. Macrophages are essential to the development of atherosclerotic plaques, as well as the perpetuation of inflammation in these lesions. These cells are also directly involved in the rupture of unstable plaques. Recently, different macrophage populations have being identified in atherosclerotic lesions. Although M2 macrophages (alternative pathway-activated macrophages, example IL-4) have been identified in lesions, the function of these cells in atherosclerosis has not been defined yet. M2 macrophages exhibit high endocytic capacity, favouring tissue remodelling and exerting anti-inflammatory activity. However, in atherosclerosis, especially in unstable plaques, intense inflammatory activity, accumulation of cellular debris and severe tissue degradation were observed. Thus, it is possible that M2 macrophages have altered function in atherosclerosis. In this project we will evaluate whether the presence of oxidized LDL alters the phenotype and function of M2 macrophages. For this purpose, we will evaluate whether the addition of lipoprotein induces 1) apoptosis; 2) secretion of inflammatory cytokines; 3) reduction in the secretion of anti-inflammatory cytokines; 4) expression of cellular activation markers and 5) alteration in gene expression of adhesion molecules and extracellular matrix. With the development of this project, we intend to better understand if M2 macrophages favour persistent inflammatory response in the presence of oxLDL and if this cell population contributes to the lack of effective anti-inflammatory mechanisms in atherosclerosis. With the results we want to clarify the role of M2 macrophages in atherosclerosis and the mechanisms involved in the pathogenesis of this disease. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

GONÇALVES, Fernanda Magalhães. Effects of oxidized LDL in M2 macrophages. Implications in atherosclerosis. 2017. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.