T Cells Are Dominant Population in Human Abdominal Aortic Aneurysms and Their Infiltration in the Perivascular Tissue Correlates With Disease Severity.

Agnieszka Sagan,Christian Delles,Pasquale Maffia,Karol Urbanski,Tomasz J Guzik,Rhian Touyz,Tomasz P Mikolajczyk,Alan Meldrum,Serena Migliarino,Kevin Daly,Boguslaw Kapelak,Neil Macritchie,Wojciech Mrowiecki,Grzegorz Filip

doi:10.3389/fimmu.2019.01979

Abstract

Abdominal Aortic Aneurysm (AAA) is a major cause of cardiovascular mortality. Adverse changes in vascular phenotype act in concert with chronic inflammation to promote AAA progression. Perivascular adipose tissue (PVAT) helps maintain vascular homeostasis but when inflamed and dysfunctional, can also promote vascular pathology. Previous studies suggested that PVAT may be an important site of vascular inflammation in AAA; however, a detailed assessment of leukocyte populations in human AAA, their anatomic location in the vessel wall and correlation to AAA size remain undefined. Accordingly, we performed in depth immunophenotyping of cells infiltrating the pathologically altered perivascular tissue (PVT) and vessel wall in AAA samples at the site of maximal dilatation (n = 51 patients). Flow cytometry revealed that T cells, rather than macrophages, are the major leukocyte subset in AAA and that their greatest accumulations occur in PVT. Both CD4+ and CD8+ T cell populations are highly activated in both compartments, with CD4+ T cells displaying the highest activation status within the AAA wall. Finally, we observed a positive relationship between T cell infiltration in PVT and AAA wall. Interestingly, only PVT T cell infiltration was strongly related to tertiles of AAA size. In summary, this study highlights an important role for PVT as a reservoir of T lymphocytes and potentially as a key site in modulating the underlying inflammation in AAA.

Highlights

Abdominal aortic aneurysm (AAA) is defined as a pathological dilatation of the aorta, to more than 1.5 times the normal diameter
Analysis of the percentage distribution of leukocyte subpopulations in AAA shows that the major subpopulation are T cells for both aneurysmal perivascular tissue (PVT) (29 ± 3%) and wall (31 ± 3%; Figure 1B) while other leukocyte subsets were less abundant, with a surprisingly low presence of macrophages in both AAA wall and PVT (Figure 1B)
Immunofluorescence staining of AAA revealed an increased presence of T cells within PVT compared with AAA wall (Figure 1C)

Summary

Introduction

Abdominal aortic aneurysm (AAA) is defined as a pathological dilatation of the aorta, to more than 1.5 times the normal diameter. AAAs are one of the most important causes of cardiovascular morbidity and mortality and occurs in up to 9% of men after 65 years of age [1]. AAA shares many of the same risk factors as atherosclerosis including advanced age, smoking, hypertension, and hypercholesterolemia [2]. It has been shown that elevated BMI increased the likelihood of AAA diagnosis [3]. The mechanisms of AAA, defined primarily in animal model studies, are complex, involving smooth muscle cell apoptosis, oxidative stress [4], and inflammation [5]. Patients with AAA have elevated circulating pro-inflammatory cytokines [6,7,8] and immunohistochemical studies of AAA reveal the presence of inflammatory cells such as macrophages, T cells, B cells, dendritic cells, natural killer cells, neutrophils, and mast cells [9,10,11,12,13,14]

Methods

Results

Conclusion