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Characterization of the inflammatory response profile in the perivascular adipose tissue associated with coronary artery disease: an autopsy study

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Author(s):
Daniela Souza Farias Itáo
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
Defense date:
Examining board members:
Claudia Kimie Suemoto; Amaro Nunes Duarte Neto; Carlos Augusto Goncalves Pasqualucci
Advisor: Claudia Kimie Suemoto
Abstract

Introduction: Inflammation in the perivascular adipose tissue (PvAT) was associated with coronary atherosclerosis in previous studies. The increase of B CD20+ lymphocyte and the CD68+ macrophage density was correlated with the percentage of arterial obstruction and CD68+ macrophage density was greater in the regions near unstable atherosclerotic plaques. However, the association with T CD3+ lymphocytes was not found. There are controversial results on what macrophage phenotype is predominant in association with atherosclerosis. There were no studies regarding the association between the Th1 and Treg lymphocyte lineages and atherosclerosis in humans, as well as investigations with unstable plaques. Aim: To investigate the characterization of inflammatory profile in the PvAT surrounding atherosclerotic plaques in coronary arteries and to compare this inflammatory profile in the periplaque PvAT with PvAT surrounding coronary arteries without atherosclerotic plaques and away from any atherosclerotic plaques (control PvAT) using autopsy material. Method: Main coronary arteries were removed from the heart with surrounding PvAT. The atherosclerotic plaque with the greatest arterial obstruction or signs of unstable plaques was sampled. Unstable lesions were preferred over stable lesions. Moreover, one segment of PvAT surrounding coronary arteries without atherosclerotic plaques and away from any atherosclerotic plaques was sampled as control. In coronary arteries, we performed morphometric measures, measured the area of components of the atherosclerotic plaque, and classified the plaques as stable or unstable. The macrophage profile (M1 CD11c+ and M2 CD206+) and T lymphocytes lineages (Th1 CD4+CXCR3+ and Tregs CD45RO+FoxP3+) were identified and quantified using simple and double immunohistochemistry technique. The correlations were tested with regression models adjusted for robust standard errors and possible confounding factors. Results: In 319 arteries and PvAT samples from 82 individuals (mean age 69,0±14,4 and 50% male), we found that the increase of M1 macrophage increased 1,95 times the risk of thrombus [p=0,03]. The pro-inflammatory profile was correlated with atherosclerotic components related to destabilization (M1: the decrease of fibrous cap [p=0,006], the increase of lipid [p=0,01], and the greater number of vasa vasorum [p=0,01]; Th1: the decrease in plaque size [p=0,02], the decrease of calcification [p=0,02], and the greater number of vasa vasorum [p=0,03]). The anti-inflammatory profile was associated with atherosclerotic components related to advanced and stable plaques (M2 e Treg, respectively: an increase in plaque size [p=0,02; p<0,001] and the increase of calcification [p=0,03; p=0,005]). Treg lymphocytes were also associated with atherosclerotic components in unstable plaques: the decrease of collagen [p=0,001] and the increase of necrosis [p=0,005]. We found an increase of M1 macrophage in the periplaque PvAT compared to control PvAT associated with the increase of collagen [p=0,03] and M2 macrophage was greatest in the periplaque PvAT in association with intima-media thickness [p=0,02]. Conclusion: We found a predominance of the pro-inflammatory profile, mainly by M1 macrophage. The pro-inflammatory profile was associated with atherosclerotic plaque components related to destabilization. The anti-inflammatory profile had the majority of associations with atherosclerotic components related to stabilization and chronic lesions, except for the Treg lymphocyte, which was also associated with atherosclerotic components related to destabilization in unstable plaques. The PvAT inflammation was heterogeneous, with greater inflammation in the PvAT surrounding coronary arteries with atherosclerosis (AU)

FAPESP's process: 17/24066-1 - CHARACTERIZATION OF THE INFLAMMATORY RESPONSE PROFILE IN THE PERIVASCULAR ADIPOSE TISSUE ASSOCIATED WITH CORONARY ARTERY DISEASE: AN AUTOPSY STUDY
Grantee:Daniela Souza Farias Itao
Support Opportunities: Scholarships in Brazil - Doctorate