Kynurenine Pathway Metabolites as Potential Clinical Biomarkers in Coronary Artery Disease

Gáspár, Renáta; Halmi, Dóra; Demján, Virág; Berkecz, Róbert; Pipicz, Márton; Csont, Tamás

doi:10.3389/fimmu.2021.768560

Cited by 50 publications

(27 citation statements)

References 149 publications

(222 reference statements)

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“…The role of the kynurenine pathway in atherosclerotic disease has been extensively reviewed [113][114][115]. A state of low-grade inflammation in atherosclerosis is marked by increased levels of IL-6, an inducer of IDO [116].…”

Section: Atherosclerosismentioning

confidence: 99%

“…A state of low-grade inflammation in atherosclerosis is marked by increased levels of IL-6, an inducer of IDO [116]. Once more, research shows that decreased tryptophan and an increased kynurenine/tryptophan-ratio is associated with the severity of atherosclerosis [113] and thus indicating that increased IDO-activity is related to this state of low-grade inflammation.…”

Section: Atherosclerosismentioning

confidence: 99%

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Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

2022

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The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing and therefore is its burden of disease as NALFD is a risk factor for cirrhosis and is associated with other metabolic conditions such as type II diabetes, obesity, dyslipidaemia and atherosclerosis. Linking these cardiometabolic diseases is a state of low-grade inflammation, with higher cytokines and c-reactive protein levels found in individuals with NAFLD, obesity and type II diabetes. A possible therapeutic target to decrease this state of low-grade inflammation is the metabolism of the essential amino-acid tryptophan. Its three main metabolic pathways (kynurenine pathway, indole pathway and serotonin/melatonin pathway) result in metabolites such as kynurenic acid, xanturenic acid, indole-3-propionic acid and serotonin/melatonin. The kynurenine pathway is regulated by indoleamine 2,3-dioxygenase (IDO), an enzyme that is upregulated by pro-inflammatory molecules such as INF, IL-6 and LPS. Higher activity of IDO is associated with increased inflammation and fibrosis in NAFLD, as well with increased glucose levels, obesity and atherosclerosis. On the other hand, increased concentrations of the indole pathway metabolites, regulated by the gut microbiome, seem to result in more favorable outcomes. This narrative review summarizes the interactions between tryptophan metabolism, the gut microbiome and the immune system as potential drivers of cardiometabolic diseases in NAFLD.

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Section: Atherosclerosismentioning

confidence: 99%

Section: Atherosclerosismentioning

confidence: 99%

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

2022

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“…Воспаление, по-видимому, является одним из основных катализаторов переключения с синтеза серотонина на кинурениновый путь, поскольку провоспалительные цитокины индуцируют активность ферментов идоламин 2,3-диоксигеназы (IDO) и триптофан 2,3-диоксигеназы (TDO), которая обычно низкая в базальных условиях [15]. Несбалансированный кинуреновый путь вовлечен в патомеханизмы различных заболеваний, включая ишемическую болезнь сердца [16].…”

Section: Conflicts Of Interestsunclassified

Analysis of changes in the serotonin inactivation coefficient in brain structures with simultaneous modeling of chronic neurogenic pain and malignant neoplasia

Котиева

Frantsiyants²,

Шлык

et al. 2022

SJCEM

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Introduction. Chronic pain syndrome in the development of malignant neoplasms has a complex polyethological character. The study of the pathogenetic mechanisms of pain during the growth of the transplanted tumor in the experiment can open up broad perspectives for the creation of new domestic analgesic drugs for use in oncology.Aim. To study the serotonin inactivation coefficient (SIC), the ratio of serotonin (S) and its main metabolite 5-hydroxyindolacetic acid (S-OH) in brain areas (cortex, hypothalamus) with simultaneous modeling of chronic neurogenic pain and malignant neoplasia.Material and Methods. The study involved white mongrel rats (males). To create a model of chronic pain (CP), ligation of the sciatic nerve was performed according to the method of V.V. Kravtsova in modification. Rat sarcoma M-1 was used to simulate malignant neoplasia. At the main stage of the study, the animals were divided into 4 groups: control, two comparison groups (model of chronic pain, standard M-1 sarcoma grafting) and experimental (combined modeling of CP and oncological process). Animals of the second, third and fourth groups were euthanized sequentially at the 2nd and 3rd weeks of the development of the tumor process.Results. Chronic pain syndrome disrupts the process of serotonin metabolism: the decrease in SIC in the cerebral cortex of experimental animals was more significant by 48% (day 14) and 72% (day 21). The development of the oncological process in comparison groups (groups 3a and 3b) is accompanied by a decrease in the level of SIC, more significant at the 21th day of M-1 sarcoma development: by 37% in the hypothalamus, by 41% in the cerebral cortex. With simultaneous modeling of chronic neurogenic pain and malignant neoplasia, the lowest values of the studied indicator were noted, the decrease was 75% in the cerebral cortex (group 4a) and 87% (group 4b).Discussion. Chronic neurogenic pain and M-1 sarcoma development in isolated modeling variants cause a significant decrease in SIC in hypothalamus and cerebral cortex due to disorders of serotonin formation. A more significant disruption of the serotonin mediator system was noted in cerebral cortex which leads to a decrease in the body's adaptive capabilities to pain and a disruption of the regulatory mechanisms of metabolism.Conclusion. Modification of serotonin metabolism can be considered as a potential therapeutic target for the treatment of chronic pain syndrome in oncology.

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“…Besides, the ratio of KYN/TRP may a sensitive pointer of rigorous coronary events for individuals displaying no history of CHD, also can be used to predict dangerous coronary events even use to determining all-cause mortality for individuals suffering from CHD ( Pedersen et al, 2011 ; Sulo et al, 2013 ). Additionally, a new review of more than 20 clinical studies also shown that the change of other TRP metabolites/TRP ratio also predict the significant CHD, so TRP pathway metabolites may as potential clinical biomarkers in CHD ( Gáspár et al, 2021 ). Our previous plasma metabolome and genome-wide association studies also found that IPA may have a potential protective effect on patients with CHD ( Wang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Tryptophan was metabolized into beneficial metabolites against coronary heart disease or prevented from producing harmful metabolites by the in vitro drug screening model based on Clostridium sporogenes

Tian

Wu²,

Cheng³

et al. 2022

Front. Microbiol.

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In our previous study of 2,130 Chinese patients with coronary heart disease (CHD), we found that tryptophan (TRP) metabolites contributed to elevated risks of death. Many TRP-derived metabolites require the participation of intestinal bacteria to produce, and they play an important role in the pathogenesis of metabolic diseases such as CHD. So it is necessary to metabolize TRP into beneficial metabolites against CHD or prevent the production of harmful metabolites through external intervention. Indole-3-butyric acid (IBA) may be a key point of gut microbiota that causes TRP metabolism disorder and affects major adverse cardiovascular events in CHD. Therefore, this study aimed to develop a method based on in vitro culture bacteria to evaluate the effects of IBA on specific microbial metabolites quickly. We detected the concentrations of TRP and its metabolites in 11 bacterial strains isolated from feces using liquid chromatography–mass spectrometry, and selected Clostridium sporogenes as the model strain. Then, IBA was used in our model to explore its effect on TRP metabolism. Results demonstrated that the optimal culture conditions of C. sporogenes were as follows: initial pH, 6.8; culture temperature, 37°C; and inoculum amount, 2%. Furthermore, we found that IBA increases the production of TRP and 5-HIAA by intervening TRP metabolism, and inhibits the production of KYNA. This new bacteria-specific in vitro model provides a flexible, reproducible, and cost-effective tool for identifying harmful agents that can decrease the levels of beneficial TRP metabolites. It will be helpful for researchers when developing innovative strategies for studying gut microbiota.

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Kynurenine Pathway Metabolites as Potential Clinical Biomarkers in Coronary Artery Disease

Cited by 50 publications

References 149 publications

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

Interactions between Tryptophan Metabolism, the Gut Microbiome and the Immune System as Potential Drivers of Non-Alcoholic Fatty Liver Disease (NAFLD) and Metabolic Diseases

Analysis of changes in the serotonin inactivation coefficient in brain structures with simultaneous modeling of chronic neurogenic pain and malignant neoplasia

Tryptophan was metabolized into beneficial metabolites against coronary heart disease or prevented from producing harmful metabolites by the in vitro drug screening model based on Clostridium sporogenes

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