Indoleamine 2,3-dioxygenase (IDO) is an important immunomodulator suppressing the activation of T lymphocytes, and its level in blood is increased in several autoimmune and inflammatory diseases. We have previously shown that this activity associates with several signs and risk factors of atherosclerosis in 24 to 39-year-old females. Now we repeat this analysis in an older population (n = 921, age range 46-76 years), i.e. in a population with more advanced atherosclerosis. IDO activity had a significant positive correlation in both sexes with carotid artery intima/media thickness (IMT), an early marker of atherosclerosis. In females, a significant negative correlation with HDL cholesterol and a positive correlation with triglycerides levels was observed. The association with IMT did not remain significant after adjustment with classical risk factors of atherosclerosis. It is thus concluded that IDO is a sensitive marker of atherosclerosis--or the inflammatory response associated with it--but does not have an independent role in the pathogenesis of this disease.

2010) Activation of indoleamine 2,3-dioxygenase-induced tryptophan degradation in advanced atherosclerotic plaques: Tampere Vascular Study, Annals of Medicine, 42:1, 55-63To link to this article: http://dx. AbstractObjective. 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 ϭ 24) and in non-atherosclerotic arteries (n ϭ 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 signifi cant (false discovery rate (FDR) ϭ 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 Ͻ 0.05 for all). Conclusions. IDO and the IDO-related pathway are important mediators of the immunoinfl ammatory responses in advanced atherosclerosis offering new viable therapeutic targets for the development of antiatherogenic immunosuppressive therapies.

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Background Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme that has an important immunomodulator function. Human inflammatory response promotes upregulation of IDO level in blood. This may lead to suppression of inflammation in atherosclerotic vessel wall and consequently may slow the progression of the disease. Previous studies have shown that IDO activity correlates with early signs of atherosclerosis especially in females but is not an atherosclerosis-specific marker. Materials and methods IDO levels were measured from females (n=544; age 24–39; weight 40.5–134.4 kg) in 2001 along with several risk factors for atherosclerosis. Follow-up risk factor measurements were performed in 2007 and 2011. Here we aimed to elucidate the relationship between IDO measurements from 2001 and several atherosclerotic risk factors from 2007 and 2011 by analyzing correlations and risk ratios from the Cardiovascular Risk in Young Finns Study patient cohort. Results After age standardization, IDO correlated significantly with BMI (p=0.0008), waist (p=0.0009) and logarithmically modified triglycerides (p=0.0488) and CRP (p=0.0014) in female samples (n=434) from 2007. When female samples (n=384) from 2011 were examined, statistically significant correlations were discovered in BMI and Waist in both unadjusted (p<0.0001 and 0.0003, respectively) and age-adjusted analysis (p=0.0007 and 0.006, respectively). In contrast, only weak correlations were found in male samples. In risk ratio analysis IDO promoted obesity (RR=1.027, p=0.01) in females (n=431) in 10-year follow-up study even after the data was adjusted for age, CRP and BMI. Conclusions It is concluded that IDO activity forecasts obesity – a well-characterized risk factor for diabetes and atherosclerosis – in premenopausal females.

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