Activation of indoleamine 2,3-dioxygenase-induced tryptophan degradation in advanced atherosclerotic plaques: Tampere Vascular Study

作者：Niinisalo Petri^*; Oksala Niku; Levula Mari; Pelto Huikko Markku; Jarvinen Otso; Salenius Juha Pekka; Kytomaki Leena; Soini Juhani T; Kahonen Mika; Laaksonen Reijo; Hurme Mikko; Lehtimaki Terho

来源：Annals of Medicine, 2010, 42(1): 55-63.

DOI：10.3109/07853890903321559

• Atherosclerosis
• gene expression
• gene-set enrichment analysis
• immunohistochemistry
• indoleamine 2,3-dioxygenase

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.

• 出版日期2010-2