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Quantification and characterization of monocytes subpopulations in human atherosclerosis

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Author(s):
Amauri da Silva Justo Júnior
Total Authors: 1
Document type: Master's Dissertation
Press: Campinas, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
Defense date:
Examining board members:
Maria Heloisa de Souza Lima Blotta; Maria Cristina de Oliveira Izar; José Roberto Matos Souza
Advisor: Maria Heloisa de Souza Lima Blotta
Abstract

Atherosclerosis is a chronic inflammatory disease characterized by the retention of lipids and immune cells in the arterial intima. Among the cells that entry in the arterial wall, the monocytes are the first to be recruited differentiating into macrophages and contributing to the formation of atheroma lesion. It is known that the circulating monocytes constitute a heterogenic population composed for three cells types, the cells CD14++CD16- (Classical), CD14++CD16+ (Intermediate) and CD14+CD16++ (Non classical) that present distinct functions and migratory capacity. The different monocytes population can be associated with the presence of risk factors to the development of coronary arterial disease (CAD) or even predict cardiovascular events in individual with CAD. However, there is not a consensus about the function of each monocyte subset. Due to the important role of monocytes in all development stages of the atheroma the aim of this study is evaluate the presence of different monocytes subpopulations in samples of peripheral blood of patients with CAD and also evaluate the cytokine production by this subsets to atherogenic antigen (HSP60). For this, the quantification and phenotypic characterization of peripheral blood monocytes of the study groups (chronic coronary syndrome (CCS), acute coronary syndrome (ACS), and controls [with (RF) and without (C) risk factors for atherosclerosis]), as well the cytokine production evaluation were done by flow cytometry. About the frequency of monocytes subpopulation, we found a lower frequency of classical and increased frequency of non classical monocytes in the SCC group compared to control group. The analysis of absolute number showed that the CCS group presents a less quantity of total monocytes and of the classical and intermediate subpopulation when compared to the control group, while the ACS group shows an increase in the quantity of these cells. In relation to the receptors analyzed, we find an increased frequency of the three CCR5+ monocytes subpopulation and CX3CR1+ non classical in the ACS group. We also find in the ACS group the higher frequency of TLR2+, TLR4+ and CD36+ cells in the three subpopulation of monocytes, what would suggest that the monocytes of these patients are able to promote inflammation in DAMP response generated on the acute. The HSP60 induced the production of inflammatory cytokines, chemokines and Th1 response modulating cytokines in classical and intermediate monocytes. In conclusion, our data highlight the role of the 3 monocytes subpopulation in all atherogenic process and its association with disease severity (AU)

FAPESP's process: 14/00327-2 - Quantification and function of monocytes subpopulations in atherosclerosis
Grantee:Amauri da Silva Justo Junior
Support Opportunities: Scholarships in Brazil - Master