Institute of Molecular Biology and Biophysics, Federal Research Center of Fundamental and Translational Medicine, Timakova Str. 2, Novosibirsk 630060, Russia.
Int J Mol Sci. 2024 Jun 25;25(13):6933. doi: 10.3390/ijms25136933.
Persistent systemic chronic inflammatory conditions are linked with many pathologies, including cardiovascular diseases (CVDs), a leading cause of death across the globe. Among various risk factors, one of the new possible contributors to CVDs is the metabolism of essential amino acid tryptophan. Proinflammatory signals promote tryptophan metabolism via the kynurenine (KYN) pathway (KP), thereby resulting in the biosynthesis of several immunomodulatory metabolites whose biological effects are associated with the development of symptoms and progression of various inflammatory diseases. Some participants in the KP are agonists of aryl hydrocarbon receptor (AhR), a central player in a signaling pathway that, along with a regulatory influence on the metabolism of environmental xenobiotics, performs a key immunomodulatory function by triggering various cellular mechanisms with the participation of endogenous ligands to alleviate inflammation. An AhR ligand with moderate affinity is the central metabolite of the KP: KYN; one of the subsequent metabolites of KYN-kynurenic acid (KYNA)-is a more potent ligand of AhR. Understanding the role of AhR pathway-related metabolites of the KP that regulate inflammatory factors in cells of the cardiovascular system is interesting and important for achieving effective treatment of CVDs. The purpose of this review was to summarize the results of studies about the participation of the KP metabolite-KYNA-and of the AhR signaling pathway in the regulation of inflammation in pathological conditions of the heart and blood vessels and about the possible interaction of KYNA with AhR signaling in some CVDs.
持续性全身慢性炎症状态与许多病理相关，包括心血管疾病（CVDs），这是全球范围内主要的致死原因。在各种风险因素中，色氨酸代谢可能是导致 CVDs 的新因素之一。促炎信号通过犬尿氨酸（KYN）途径（KP）促进色氨酸代谢，从而导致几种免疫调节代谢物的生物合成，其生物学效应与各种炎症性疾病的症状发展和进展相关。KP 的一些参与者是芳香烃受体（AhR）的激动剂，AhR 是信号通路的核心参与者，除了对环境外来物代谢的调节作用外，通过参与内源性配体的各种细胞机制发挥关键的免疫调节功能，从而减轻炎症。KP 的具有中等亲和力的中央代谢物是 KYN；KYN 的随后代谢物之一——犬尿氨酸酸（KYNA）——是 AhR 的更有效配体。了解 KP 相关代谢物调节心血管系统细胞中炎症因子的 AhR 通路的作用，对于实现 CVDs 的有效治疗是有趣且重要的。本文综述了关于 KP 代谢物-KYNA-和 AhR 信号通路在心脏和血管病理条件下调节炎症的作用，以及 KYNA 与某些 CVDs 中 AhR 信号相互作用的研究结果。
