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Your search keyword '"Kassiteridi, Christina"' showing total 2 results
Start Over Author "Kassiteridi, Christina" Publisher oxford university press
2 results on '"Kassiteridi, Christina"'

1. Immune cell census in murine atherosclerosis: cytometry by time of flight illuminates vascular myeloid cell diversity

Author

Cole, Jennifer E., Park, Inhye, Ahern, David, Kassiteridi, Christina, Danso Abeam, Dina, Goddard, Michael, Green, Patricia, Maffia, Pasquale, Monaco, Claudia, Cole, Jennifer E., Park, Inhye, Ahern, David J., Kassiteridi, Christina, Abeam, Dina Danso, Goddard, Michael E., Green, Patricia, Maffia, Pasquale, and Monaco, Claudia

Subjects
Mice, Knockout, ApoE, Macrophage, Physiology, Aortic Diseases, Cell Separation, Antigen-Antibody Complex, Diet, High-Fat, Immunophenotyping, Mice, Vascular, Physiology (medical), Animals, Myeloid Cells, Aorta, Immunity and Inflammation, Immune cell, Spectrophotometry, Atomic, Macrophages, Immune cells, Censuses, Original Articles, Cytometry by time of flight, Flow Cytometry, Atherosclerosis, Plaque, Atherosclerotic, Disease Models, Animal, Editor's Choice, Phenotype, Atherosclerosi, Cardiology and Cardiovascular Medicine, Biomarkers
Abstract

Aims: \ud Atherosclerosis is characterised by the abundant infiltration of myeloid cells starting at early stages of disease. Myeloid cells are key players in vascular immunity during atherogenesis. However, the subsets of vascular myeloid cells have eluded resolution due to shared marker expression and atypical heterogeneity in vascular tissues. We applied the high-dimensionality of mass cytometry to the study of myeloid cell subsets in atherosclerosis.\ud \ud Methods and Results: \ud Apolipoprotein E-deficient (ApoE-/-) mice were fed a chow or a high fat (western) diet for 12 weeks. Single cell aortic preparations were probed with a panel of 35 metal-conjugated antibodies using Cytometry by time of flight (CyTOF). Clustering of marker expression on live CD45+ cells from the aortas of ApoE-/- mice identified 13 broad populations of leucocytes. Monocyte, macrophage, type 1 and type 2 conventional dendritic cell (cDC1 and cDC2), plasmacytoid dendritic cell (pDC), neutrophil, eosinophil, B cell, CD4+ and CD8+ T cell, γδ T cell, natural killer (NK) cell and innate lymphoid (ILC) cell populations accounted for approximately 95% of the live CD45+ aortic cells. Automated clustering algorithms applied to the Lin-CD11blo-hi cells revealed 20 clusters of myeloid cells. Comparison between chow and high fat fed animals revealed increases in monocytes (both Ly6C+ and Ly6C-), pDC and a CD11c+ macrophage subset with high fat feeding. Concomitantly, the proportions of CD206+ CD169+ subsets of macrophages were significantly reduced as were cDC2.\ud \ud Conclusions: \ud A CyTOF-based comprehensive mapping of the immune cell subsets within atherosclerotic aortas from ApoE-/- mice offers tools for myeloid cell discrimination within the vascular compartment and it reveals that high fat feeding skews the myeloid cell repertoire towards inflammatory monocyte-macrophage populations rather than resident macrophage phenotypes and cDC2 during atherogenesis.

Published
2018

2. Interferon regulatory factor-5-dependent CD11c+ macrophages contribute to the formation of rupture-prone atherosclerotic plaques.

Author

Edsfeldt A, Swart M, Singh P, Dib L, Sun J, Cole JE, Park I, Al-Sharify D, Persson A, Nitulescu M, Borges PDN, Kassiteridi C, Goddard ME, Lee R, Volkov P, Orho-Melander M, Maegdefessel L, Nilsson J, Udalova I, Goncalves I, and Monaco C

Subjects
Animals, Apolipoproteins E genetics, Humans, Inflammation metabolism, Mice, Necrosis, Atherosclerosis metabolism, Atherosclerosis pathology, Interferon Regulatory Factors metabolism, Macrophages immunology, Plaque, Atherosclerotic metabolism, Plaque, Atherosclerotic pathology
Abstract

Aims: Inflammation is a key factor in atherosclerosis. The transcription factor interferon regulatory factor-5 (IRF5) drives macrophages towards a pro-inflammatory state. We investigated the role of IRF5 in human atherosclerosis and plaque stability., Methods and Results: Bulk RNA sequencing from the Carotid Plaque Imaging Project biobank were used to mine associations between major macrophage associated genes and transcription factors and human symptomatic carotid disease. Immunohistochemistry, proximity extension assays, and Helios cytometry by time of flight (CyTOF) were used for validation. The effect of IRF5 deficiency on carotid plaque phenotype and rupture in ApoE-/- mice was studied in an inducible model of plaque rupture. Interferon regulatory factor-5 and ITGAX/CD11c were identified as the macrophage associated genes with the strongest associations with symptomatic carotid disease. Expression of IRF5 and ITGAX/CD11c correlated with the vulnerability index, pro-inflammatory plaque cytokine levels, necrotic core area, and with each other. Macrophages were the predominant CD11c-expressing immune cells in the plaque by CyTOF and immunohistochemistry. Interferon regulatory factor-5 immunopositive areas were predominantly found within CD11c+ areas with a predilection for the shoulder region, the area of the human plaque most prone to rupture. Accordingly, an inducible plaque rupture model of ApoE-/-Irf5-/- mice had significantly lower frequencies of carotid plaque ruptures, smaller necrotic cores, and less CD11c+ macrophages than their IRF5-competent counterparts., Conclusion: Using complementary evidence from data from human carotid endarterectomies and a murine model of inducible rupture of carotid artery plaque in IRF5-deficient mice, we demonstrate a mechanistic link between the pro-inflammatory transcription factor IRF5, macrophage phenotype, plaque inflammation, and its vulnerability to rupture., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Published
2022
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