Journal
ANNALS OF MEDICINE
Volume 42, Issue 1, Pages 55-63Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/07853890903321559
Keywords
Atherosclerosis; gene expression; gene-set enrichment analysis; immunohistochemistry; indoleamine 2,3-dioxygenase
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Funding
- European Union [201668]
- AtheroRemo
- Tampere University Hospital
- Emil Aaltonen Foundation
- Finnish Cultural Foundation
- Research Foundation of Orion Corporation
- Jenny and Antti Wihuri Foundation
- Academy of Finland [104821]
- Finnish Angiology association
- Maire Taponen Foundation
- Paavo Nurmi Foundation
- Academy of Finland (AKA) [104821, 104821] Funding Source: Academy of Finland (AKA)
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Objective. We aimed to characterize the expression of indoleamine 2,3-dioxygenase (IDO) or IDO-induced tryptophan degradation-dependent pathways, which may lead to suppression of T cells and possible protection against atherosclerosis. Methods and results. Expression of IDO and IDO-related pathway components was analyzed in advanced human atherosclerotic plaques (n = 24) and in non-atherosclerotic arteries (n = 6). Up-regulation of IDO and genes related to the IDO pathway was found to be pronounced in atherosclerotic plaques. Immunohistochemistry demonstrated IDO protein in the atheromatous core and co-distribution with monocyte-macrophages (CD68-positive cells). In gene-set enrichment analysis, the IDO pathway revealed a significant (false discovery rate (FDR) = 0.07) regulatory T cell, fork-head box protein 3 (FoxP3)-initiated CD28-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-inducible T cell co-stimulator (ICOS)-driven pathway leading to activation of IDO expression in antigen-presenting cells (APCs). Expression of these IDO pathway genes varied between 2.1- and 16.8-fold as compared to control tissues (P < 0.05 for all). Conclusions. IDO and the IDO-related pathway are important mediators of the immunoinflammatory responses in advanced atherosclerosis offering new viable therapeutic targets for the development of antiatherogenic immunosuppressive therapies.
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