Impairment of Kynurenine Metabolism in Cardiovascular Disease

Rudzite, Vera; Sileniece, G.; Liepina, D.; Dalmane, A.; Zirne, R.

doi:10.1007/978-1-4684-5952-4_89

Cited by 21 publications

(15 citation statements)

References 6 publications

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“…Patients with atheromatous plaques show lower serum tryptophan compared to healthy controls [83,84]. Additionally, lower serum tryptophan and higher kynurenine concentrations compared to healthy controls were reported from patients suffering from myocardial infarction or angina pectoris after an oral load with L-tryptophan [83].…”

Section: Tryptophan Degradationmentioning

confidence: 97%

“…Additionally, lower serum tryptophan and higher kynurenine concentrations compared to healthy controls were reported from patients suffering from myocardial infarction or angina pectoris after an oral load with L-tryptophan [83]. The rate of tryptophan degradation expressed by the ratio of the first product -kynurenine -and the substrate of IDO -tryptophan (kynurenine to tryptophan ratio, kyn/trp), allows a good estimate of IDO activity [84].…”

Section: Tryptophan Degradationmentioning

confidence: 98%

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Crucial Role of Interferon-γ and Stimulated Macrophages in Cardiovascular Disease

Schroecksnadel

Frick²,

Winkler³

et al. 2006

CVP

126

102

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Inflammation and immune activation are crucially involved in the pathogenesis of atherosclerosis and cardiovascular disease. Accordingly, markers of inflammation such as fibrinogen, ferritin, C-reactive protein or neopterin are found in patients with vascular diseases, correlating strongly with the extent of disease and predicting disease progression. Neopterin formation by human monocyte-derived macrophages and dendritic cells is induced by the pro-inflammatory cytokine interferon-gamma, which is released by activated T-lymphocytes. Human macrophages are centrally involved in plaque formation, and interferon-gamma and macrophages are also of importance in the development of oxidative stress for antimicrobial and antitumoural defence within the cell-mediated immune response. Interferon-gamma also stimulates the enzyme indoleamine-2,3-dioxygenase, which degrades tryptophan to kynurenine. Again, macrophages are the most important cell type executing this enzyme reaction, but also other cells like dendritic cells, endothelial cells or fibroblasts can contribute to the depletion of tryptophan. Likewise, enhanced tryptophan degradation was reported in patients with coronary heart disease and was found to correlate with enhanced neopterin formation. In chronic diseases such as in cardiovascular disease, biochemical reactions induced by interferon-gamma may have detrimental consequences for host cells. In concert with other pro-inflammatory cytokines, interferon-gamma is the most important trigger for the formation and release of reactive oxygen species (ROS). Chronic ROS-production leads to the depletion of antioxidants like vitamin C and E and glutathione, with a consequence that oxidative stress develop. Oxidative stress plays a major role in the atherogenesis and progression of cardiovascular disease, and it may also account for the irreversible oxidation of other oxidation-sensitive substances like B-vitamins (e.g. folic acid and B12). They are essential cofactors in homocysteine-methionine metabolism. Associations between moderate hyperhomocysteinaemia and cellular immune activation are found in several diseases including coronary heart disease, and data indicate that hyperhomocysteinaemia may develop as a consequence of immune activation. Homocysteine accumulation in the blood is established as an independent risk factor for cardiovascular disease. Homocysteine itself has the capacity to further enhance oxidative stress. Interferon-gamma appears to be a central player in atherogenesis and in the development and progression of cardiovascular disease. Anti-inflammatory and immunosuppressive treatment (e.g. with non-steroidal anti-inflammatory drugs or statins) may among other consequences, also contribute to a slow-down of the adverse effects of interferon-gamma.

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Section: Tryptophan Degradationmentioning

confidence: 97%

Section: Tryptophan Degradationmentioning

confidence: 98%

Crucial Role of Interferon-γ and Stimulated Macrophages in Cardiovascular Disease

Schroecksnadel

Frick²,

Winkler³

et al. 2006

CVP

126

102

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“…In another study, an oral load of L-Trp caused patients with myocardial infarction or angina pectoris to have higher KTR as compared to controls, indicating higher Trp degradation in these patients(180). The positive correlation between IDO activity and age was to be expected, as IDO activity is known to increase with age(181, 182).…”

Section: The Abnormal Kynurenine Pathway Links Oxidative Stress Imentioning

confidence: 99%

Tryptophan-kynurenine pathway is dysregulated in inflammation and immune activation

Liu²,

et al. 2015

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The kynurenine (Kyn) pathway is the major route for tryptophan (Trp) metabolism, and it contributes to several fundamental biological processes. Trp is constitutively oxidized by tryptophan 2, 3-dioxygenase in liver cells. In other cell types, it is catalyzed by an alternative inducible indoleamine-pyrrole 2, 3-dioxygenase (IDO) under certain pathophysiological conditions, which consequently increases the formation of Kyn metabolites. IDO is up-regulated in response to inflammatory conditions as a novel marker of immune activation in early atherosclerosis. Besides, IDO and the IDO-related pathway are important mediators of the immunoinflammatory responses in advanced atherosclerosis. In particular, Kyn, 3-hydroxykynurenine, and quinolinic acid are positively associated with inflammation, oxidative stress (SOX), endothelial dysfunction, and carotid artery intima-media thickness values in end-stage renal disease patients. Moreover, IDO is a potential novel contributor to vessel relaxation and metabolism in systemic infections, which is also activated in acute severe heart attacks. The Kyn pathway plays a key role in the increased prevalence of cardiovascular disease by regulating inflammation, SOX, and immune activation.

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“…Patients with atheromatous plaques showed lower serum tryptophan compared with healthy controls [22]. After an oral load with -tryptophan lower serum tryptophan and higher kynurenine concentrations compared with healthy controls were reported from patients suffering from myocardial infarction or angina pectoris [23].…”

Section: Introductionmentioning

confidence: 97%

Immune activation and degradation of tryptophan in coronary heart disease

Wirleitner

Rudzite²,

Neurauter

et al. 2003

Eur J Clin Investigation

Self Cite

178

105

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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.

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Impairment of Kynurenine Metabolism in Cardiovascular Disease

Cited by 21 publications

References 6 publications

Crucial Role of Interferon-γ and Stimulated Macrophages in Cardiovascular Disease

Crucial Role of Interferon-γ and Stimulated Macrophages in Cardiovascular Disease

Tryptophan-kynurenine pathway is dysregulated in inflammation and immune activation

Immune activation and degradation of tryptophan in coronary heart disease

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Impairment of Kynurenine Metabolism in Cardiovascular Disease

Cited by 21 publications

References 6 publications

Crucial Role of Interferon-&#947; and Stimulated Macrophages in Cardiovascular Disease

Crucial Role of Interferon-&#947; and Stimulated Macrophages in Cardiovascular Disease

Tryptophan-kynurenine pathway is dysregulated in inflammation and immune activation

Immune activation and degradation of tryptophan in coronary heart disease

Contact Info

Product

Resources

About

Crucial Role of Interferon-γ and Stimulated Macrophages in Cardiovascular Disease

Crucial Role of Interferon-γ and Stimulated Macrophages in Cardiovascular Disease