T cells are dominant population in human abdominal aortic aneurysms and their infiltration in the perivascular tissue correlates with disease severity

Sagan, A. et al. (2019) T cells are dominant population in human abdominal aortic aneurysms and their infiltration in the perivascular tissue correlates with disease severity. Frontiers in Immunology, 10, 1979. (doi: 10.3389/fimmu.2019.01979) (PMID:31552015) (PMCID:PMC6736986)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maffia, Professor Pasquale and Mikolajczyk, Dr Tomasz and Guzik, Professor Tomasz and Migliarino, Ms Serena and Sagan, Ms Agnieszka and Daly, Mr Kevin and Meldrum, Mr Alan and MacRitchie, Dr Neil and Touyz, Professor Rhian
Authors: Sagan, A., Mikolajczyk, T., Mrowiecki, W., Macritchie, N. A., Daly, K., Meldrum, A., Migliarino, S., Urbanski, K., Filip, G., Kapelak, B., Maffia, P., Touyz, R. M., and Guzik, T. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Research Centre:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:Frontiers in Immunology
Publisher:Frontiers Media
ISSN:1664-3224
ISSN (Online):1664-3224
Copyright Holders:Copyright © 2019 Sagan, Mikolajczyk, Mrowiecki, MacRitchie, Daly, Meldrum, Migliarino, Delles, Urbanski, Filip, Kapelak, Maffia, Touyz and Guzik
First Published:First published in Frontiers in Immunology 10:1979
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES
644661In Situ Nanoparticle Assemblies for Healthcare Diagnostics and TherapyPasquale MaffiaEngineering and Physical Sciences Research Council (EPSRC)EP/L014165/1III -IMMUNOLOGY