ArticleJournal of atherosclerosis and thrombosis2021
Upregulated Kynurenine Pathway Enzymes in Aortic Atherosclerotic Aneurysm: Macrophage Kynureninase Downregulates Inflammation.
Article in Journal of atherosclerosis and thrombosis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 19 citations in OpenAlex.
- VSMC-derived 3HAA activates AhR to drive abdominal aortic aneurysm formation via the p62-Nrf2 axis.Redox biology · 2026Article
- Integrated multi-omics analysis reveals a gut microbiota-tryptophan metabolism axis contributes to sex differences in a β-aminopropionitrile-induced aortic dissection mouse model.Biology of sex differences · 2026Article
- Identification of potential biomarkers of tryptophan metabolism in Kawasaki disease and exploration of potential mechanisms.Translational pediatrics · 2026Article
- The Role of Downstream Kynurenine Pathway Metabolites in the Modulation of Cardiovascular Disease Development in Chronic Kidney Disease.International journal of tryptophan research : IJTR · 2026Review
- The tryptophan-kynurenine pathway in cardiovascular diseases: mechanistic insights and therapeutic opportunities.Frontiers in cardiovascular medicine · 2026Review
- Serum metabolites and risk of aortic dissection: a two-sample Mendelian randomization study.Indian journal of thoracic and cardiovascular surgery · 2025Article
- Mechanisms of metabolic reprogramming in abdominal aortic aneurysm.Frontiers in cell and developmental biology · 2025Review
- The role of the kynurenine pathway in cardiovascular disease.Frontiers in cardiovascular medicine · 2024Review
- Macrophage in Sporadic Thoracic Aortic Aneurysm and Dissection: Potential Therapeutic and Preventing Target.Reviews in cardiovascular medicine · 2023Review
- Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.Journal of hematology & oncology · 2023Review
- Small molecule metabolites: discovery of biomarkers and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- IDO promotes the proliferation and invasion of prostate cancer cells through KYNU.Genes & genomics · 2023Article
- Targeting metabolism in aortic aneurysm and dissection: from basic research to clinical applications.International journal of biological sciences · 2023Review
- Metabolomic Profiling of Angiotensin-II-Induced Abdominal Aortic Aneurysm in LdlrInternational journal of molecular sciences · 2022Article
- The Footprint of Kynurenine Pathway in Cardiovascular Diseases.International journal of tryptophan research : IJTR · 2022Review
- Tryptophan: From Diet to Cardiovascular Diseases.International journal of molecular sciences · 2021Review
- Tryptophan Catabolism and Inflammation: A Novel Therapeutic Target For Aortic Diseases.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsInflammation and hypertension contribute to the progression of atherosclerotic aneurysm in the aorta. Vascular cell metabolism is regarded to modulate atherogenesis, but the metabolic alterations that occur in atherosclerotic aneurysm remain unknown. The present study aimed to identify metabolic pathways and metabolites in aneurysmal walls and examine their roles in atherogenesis.
methodsGene expression using microarray and metabolite levels in the early atherosclerotic lesions and aneurysmal walls obtained from 42 patients undergoing aortic surgery were investigated (early lesion n=11, aneurysm n=35) and capillary electrophoresis-time-of-flight mass spectrometry (early lesion n=14, aneurysm n=38). Using immunohistochemistry, the protein expression and localization of the identified factors were examined (early lesion n=11, non-aneurysmal advanced lesion n=8, aneurysm n=11). The roles of the factors in atherogenesis were analyzed in macrophages derived from human peripheral blood mononuclear cells.
resultsEnrichment analysis using 35 significantly upregulated genes (log2 ratio, ＞3) revealed the alteration of the kynurenine pathway. Metabolite levels of tryptophan, kynurenine, and quinolinic acid and the kynurenine-to-tryptophan ratio were increased in the aneurysmal walls. Gene and protein expression of kynureninase and kynurenine 3-monooxygenase were upregulated and localized in macrophages in the aneurysmal walls. The silencing of kynureninase in the cultured macrophages enhanced the expression of interleukin-6 and indoleamine 2,3-dioxygenase 1.
conclusionOur study suggests the upregulation of the kynurenine pathway in macrophages in aortic atherosclerotic aneurysm. Kynureninase may negatively regulate inflammation via the kynurenine pathway itself in macrophages.
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Registered trials
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