Tryptophan metabolite as predictive biomarkers for prognosis of ischemic heart Disease
DOI:
https://doi.org/10.32792/jmed.2025.29.25Keywords:
Ischemic heart disease, Tryptophan, KMO, 3HAAOAbstract
Ischemic heart diseases (IHD) a condition that happens when the heart doesn'tget enough blood. Inflammation is the underlying common mechanism
involved in IHD. Kynurenine pathway, as a major route of tryptophan
degradation, its metabolites have been revealed to be crucial in CVD and
involved in several biological processes such as immune-regulation,
inflammation, and metabolism. Different enzymes have been shown to
participate in the kynurenine pathway such as KMO, 3-HHAO. The study
aimed to identify whether the metabolites of tryptophan degradation have an
association with development of inflammatory event of IHD and its progress A
case-control study was conducted at cardiac center in Thi-Qar Governorate,
with participants:90 patients with IHD divided into 3 groups, myocardial
infraction (M, n=30), angina (AN, n=30) and heart failure (HF, n=30. A 60
sample (n=60) were collected from healthy people as control group. KMO, and
3HHAO were identified by ELISA, while tryptophan concentration was
measured by HPLC technique. Statistical tests were applied by using one-way
ANOVA and ROC curve analysis. Tryptophan concentration was decreased
significantly (P value < 0.001) in patient groups compared to control group.
The levels of KMO and 3-HHAO were significantly elevated (P value <
0.001) in patients than control. These findings suggest inflammatory events
in IHD induced tryptophan catabolism through the kynurenine pathway which
plays a significant role in modulating immune response and influencing the
development of CVD.
References
Fouad GI. Synergistic anti-atherosclerotic role of combined treatment of omega-3 and co-enzyme Q10 in hypercholesterolemia-induced
obese rats. Heliyon. 2020;6(4). https://doi.org/10.1016/j.heliyon.2020.e03659
Liu L, He Y, Huang G, Zeng Y, Lu J, He R, et al. Global burden of ischemic heart disease in older adult populations linked to non
optimal temperatures: past (1990–2021) and future (2022–2050) analysis. Frontiers in Public Health. 2025;13:1548215.
https://doi.org/10.3389/fpubh.2025.1548215
Ling Z-N, Jiang Y-F, Ru J-N, Lu J-H, Ding B, Wu J. Amino acid metabolism in health and disease. Signal Transduction and Targeted
Therapy. 2023;8(1):345. https://doi.org/10.1038/s41392-023-01569-
Anand SK, Governale T-A, Zhang X, Razani B, Yurdagul Jr A, Pattillo CB, et al. Amino acid metabolism and atherosclerotic
cardiovascular disease. The American Journal of Pathology. 2024;194(4):510-24. https://doi.org/10.1016/j.ajpath.2023.12.006
Zhenyukh O, González‐Amor M, Rodrigues‐Diez RR, Esteban V, Ruiz‐Ortega M, Salaices M, et al. Branched‐chain amino acids
promote endothelial dysfunction through increased reactive oxygen species generation and inflammation. Journal of cellular and molecular
medicine. 2018;22(10):4948-62. https://doi.org/10.1111/jcmm.13759
Zhang J, Jiang X, Pang B, Li D, Kang L, Zhou T, et al. Association between tryptophan concentrations and the risk of developing
cardiovascular diseases: a systematic review and meta-analysis. Nutr Metab (Lond). 2024;21(1):82. https://doi.org/10.1186/s12986-024
-1
Paeslack N, Mimmler M, Becker S, Gao Z, Khuu MP, Mann A, et al. Microbiota-derived tryptophan metabolites in vascular
inflammation and cardiovascular disease. Amino Acids. 2022;54(10):1339-56. https://doi.org/10.1007/s00726-022-03161-5
Nitz K, Lacy M, Atzler D. Amino acids and their metabolism in atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology.
;39(3):319-30. https://doi.org/10.1161/ATVBAHA.118.311572
Chistiakov DA, Orekhov AN, Bobryshev YV. Cardiac extracellular vesicles in normal and infarcted heart. International journal of
molecular sciences. 2016;17(1):63. https://doi.org/10.3390/ijms17010063
Vécsei L, Szalárdy L, Fülöp F, Toldi J. Kynurenines in the CNS: recent advances and new questions. Nature reviews Drug discovery.
;12(1):64-82. https://doi.org/10.1038/nrd3793
Nichols M, Townsend N, Scarborough P, Rayner M. Cardiovascular disease in Europe 2014: epidemiological update. European heart
journal. 2014;35(42):2950-9. https://doi.org/10.1093/eurheartj/ehu299
N Orekhov A. Editorial (thematic issue: mechanisms of atherogenesis and development of anti-atherosclerotic therapy). Current
Pharmaceutical Design. 2015;21(9):1103-6. https://doi.org/10.2174/138161282109150103213605
Tabas I, Williams KJ, Borén J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic
implications. Circulation. 2007;116(16):1832-44. https://doi.org/10.1161/CIRCULATIONAHA.106.6768
Liu G, Chen S, Zhong J, Teng K, Yin Y. Crosstalk between tryptophan metabolism and cardiovascular disease, mechanisms, and
therapeutic implications. Oxid Med Cell Longev. 2017; 2017: 1602074.
https://doi.org/10.1155/2017/1602074
Soehnlein O, Libby P. Targeting inflammation in atherosclerosis—from experimental insights to the clinic. Nature reviews Drug
discovery. 2021;20(8):589-610. https://doi.org/10.1038/s41573-021-00198-1
Taleb S. Tryptophan dietary impacts gut barrier and metabolic diseases. Frontiers in immunology. 2019;10:2113.
https://doi.org/10.3389/fimmu.2019.02113
Frostegård J. Immunity, atherosclerosis and cardiovascular disease. BMC Med. 2013;11:117. http://www.biomedcentral.com/1741
/11/117
Mangge H, Stelzer I, Reininghaus EZ, Weghuber D, Postolache TT, Fuchs D. Disturbed tryptophan metabolism in cardiovascular
disease. Curr Med Chem. 2014;21(17):1931-7. https://doi.org/10.2174/0929867321666140304105526
Yang Y, Liu X, Liu X, Xie C, Shi J. The role of the kynurenine pathway in cardiovascular disease. Front Cardiovasc Med.
;11:1406856. https://doi.org/10.3389/fcvm.2024.1406856
Li M, Kwok MK, Fong SSM, Schooling CM. Effects of tryptophan, serotonin, and kynurenine on ischemic heart diseases and its risk
factors: a Mendelian Randomization study. Eur J Clin Nutr. 2020;74(4):613-21. https://doi.org/10.1038/s41430-020-0588-5 events in older
Sulo G, Vollset SE, Nygård O, Midttun Ø, Ueland PM, Eussen SJ, et al. Neopterin and kynurenine-tryptophan ratio as predictors of
coronary adults, https://doi.org/10.1016/j.ijcard.2012.12.090 the Hordaland Health Study. Int J Cardiol. 2013;168(2):1435-40.
Chen Y, Zhang J, Yang Y, Xiang K, Li H, Sun D, et al. Kynurenine-3-monooxygenase (KMO): From its biological functions to
therapeutic effect in diseases progression. J Cell Physiol. 2022;237(12):4339-55.
https://doi.org/10.1002/jcp.30876
Hughes TD, Güner OF, Iradukunda EC, Phillips RS, Bowen JP. The Kynurenine Pathway and Kynurenine 3-Monooxygenase
Inhibitors. Molecules. 2022;27(1). https://doi.org/10.3390/molecules27010273
Baumgartner R, Forteza MJ, Ketelhuth DFJ. The interplay between cytokines and the Kynurenine pathway in inflammation and
atherosclerosis. Cytokine. 2019;122:154148. https://doi.org/10.1016/j.cyto.2017.09.004
Dehhaghi M, Kazemi Shariat Panahi H, Guillemin GJ. Microorganisms, tryptophan metabolism, and kynurenine pathway: a complex
interconnected loop influencing human health status. International journal of tryptophan research. 2019;12:1178646919852996.
https://doi.org/10.1177/1178646919852996
Wang Y, Zhang Y, Wang W, Zhang Y, Dong X, Liu Y. Diverse Physiological Roles of Kynurenine Pathway Metabolites: Updated
Implications for Health and Disease. Metabolites. 2025;15(3). https://doi.org/10.3390/metabo15030210
Wentworth R. The Therapeutic Potential for HAAO Inhibition in Aging and Disease: The University of Arizona; 2022.
http://rightsstatements.org/vocab/InC/1.0/
Savitz J. The kynurenine pathway: a finger in every pie. Mol Psychiatry. 2020;25(1):131-47. https://doi.org/10.1038/s41380-019
-4
Donia T, Khamis A. Management of oxidative stress and inflammation in cardiovascular diseases: mechanisms and challenges.
Environmental Science and Pollution Research. 2021;28(26):34121-53. https://doi.org/10.1007/s11356-021-14109-9
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Ali Jabbar Maeedi , Anwar Jasib Thaaban Almzaiel
This work is licensed under a Creative Commons Attribution 4.0 International License.
