Immune activation and degradation of tryptophan in coronary heart disease

Abstract

Decreased tryptophan concentrations were found in a significant proportion of coronary heart disease patients and coincided with increased kyn trp-1 and also with increased neopterin concentrations, indicating an activated cellular immune response. We conclude that in coronary heart disease immune activation is associated with an increased rate of tryptophan degradation and thereby lowered tryptophan levels. Results may provide a basis for a better understanding of the pathogenesis of mood disturbances and depression in coronary heart disease patients.

Plasma Indoleamine 2,3-Dioxygenase Concentration is Increased in Hemodialysis Patients and May Contribute to the Pathogenesis of Coronary Heart Disease

“…[3][4][5][6] Currently, it is known that IDO is expressed in atherosclerotic plaques in humans 13 and some studies suggest that IDO affects directly the development of atherosclerosis. IDO activity is increased in patients with CHD and normal renal function 14 and is correlated with carotid intima-media thickness in young females. 15 Additionally, increased kynurenine to tryptophan ratio is associated with an increased risk for a major coronary event or death in patients with stable CHD.…”

“…Currently, it is known that IDO is expressed in the atherosclerotic plaques in humans 13 and some studies suggest that IDO affects directly the development of atherosclerosis. [14][15][16][17] The available studies in HD patients showed increased IDO activity, which was increased further in HD patients with atherosclerotic lesions. [3][4][5][6] However, these studies evaluated IDO activity very indirectly by estimating the serum kynurenine to tryptophan ratio.…”

Medical significance of simultaneous application of red blood cell distribution width (RDW) and neopterin as diagnostic/prognostic biomarkers in clinical practice

“…Another interesting epiphenomenon is that low serum tryptophan and the kynurenine to tryptophan ratio (Kyn/ Trp) could be predictors of acute coronary and cardiovascular events and are associated with higher mortality in patients with CVD [63,69,80,84]. The explanation of this phenomenon is related to the inverse relationship found between serum neopterin and tryptophan: low serum tryptophan concentrations are associated with high levels of the inflammatory biomarker neopterin and with elevated hsCRP [69] which results from a parallel induction of neopterin formation and tryptophan breakdown by the interferon-inducible enzyme indoleamine 2,3-dioxygenase 1 (IDO-1).…”

In Vitro Testing for Antiinflammatory Properties of Compounds

“…Both neopterin production and tryptophan degradation are induced by interferon-␥ in macrophages; thus, both reflect macrophage activity. In coronary heart disease, increases in neopterin concentrations not only correlate with tryptophan degradation (9 ) and with the activity of the disease (9 ), they also predict coronary events more sensitively than do methods such as the more widely used C-reactive protein measurements (10,11 ). By contrast, studies on the involvement of cytokines such as IL-1, IL-6, and TNF-␣ in atherogenesis stem almost exclusively from in vitro experiments.…”