Zhang Xiaolin, Qiu Miaohan, Na Kun, Cheng Minghui, Song Haixu, Zhao Ning, Liu Dan, Yan Chenghui, Han Yaling
State Key Laboratory of Frigid Zone Cardiovascular Disease, Cardiovascular Research Institute, Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China.
Cardiovasc Ther. 2025 Jul 17;2025:9123654. doi: 10.1155/cdr/9123654. eCollection 2025.
The tryptophan/kynurenic acid (KYNA) pathway plays a crucial role by modulating inflammation, oxidative stress, and immune activation. The clinical value of tryptophan metabolites in the KYNA pathway for the early diagnosis and prognosis of STEMI patients, as well as the underlying functional mechanisms, remains to be elucidated. This study evaluated the prognostic value of KYNA, a metabolite of the tryptophan pathway, in STEMI patients. Untargeted metabolomics by H-nuclear magnetic resonance (NMR) analysis was used to examine metabolite changes between 50 control subjects and 50 STEMI patients with an onset time of < 3 h. Furthermore, targeted metabolomic analysis was employed to investigate the association between KYNA and the prognosis of STEMI patients by LC-Q-TOF MS analysis. Fifteen differential metabolites were identified between STEMI patients and control subjects by H-NMR analysis. KYNA as an important metabolite upregulated obviously in the tryptophan pathway was 337.67 nmol/L in STEMI patients (interquartile range: 241.16-500.29 nmol/L). In addition, KYNA was significantly associated with major adverse cardiovascular events (MACEs) (HR: 5.95, 95% CI: 2.03-17.44; = 0.0012) and all-cause mortality (HR: 7.11, 95% CI: 1.52-33.29; = 0.013) and showed moderate predictive value for 12-month MACE (area under the curve (AUC) = 0.72, 95% CI: 0.65-0.80) and all-cause mortality (AUC = 0.74, 95% CI: 0.65-0.83). KAT1 expression was upregulated in infiltrating macrophages of thrombus tissue coming from the culprit coronary artery of STEMI patients. KAT1 upregulation was also observed in macrophages located within the peri-infarct myocardium. The KYNA level may correspond to the underlying status of acute myocardial infarction and is a promising biomarker for predicting STEMI progression.
色氨酸/犬尿喹啉酸（KYNA）途径通过调节炎症、氧化应激和免疫激活发挥关键作用。KYNA途径中色氨酸代谢产物对ST段抬高型心肌梗死（STEMI）患者早期诊断和预后的临床价值及其潜在功能机制仍有待阐明。本研究评估了色氨酸途径代谢产物KYNA对STEMI患者的预后价值。采用氢核磁共振（NMR）分析的非靶向代谢组学方法检测了50名对照受试者和50名发病时间<3小时的STEMI患者之间的代谢产物变化。此外，采用靶向代谢组学分析通过液相色谱-四极杆飞行时间质谱（LC-Q-TOF MS）分析研究KYNA与STEMI患者预后的关系。通过H-NMR分析在STEMI患者和对照受试者之间鉴定出15种差异代谢产物。KYNA作为色氨酸途径中明显上调的重要代谢产物，在STEMI患者中的水平为337.67 nmol/L（四分位间距：241.16 - 500.29 nmol/L）。此外，KYNA与主要不良心血管事件（MACE）显著相关（风险比：5.95，95%置信区间：2.03 - 17.44；P = 0.0012）和全因死亡率（风险比：7.11，95%置信区间：1.52 - 33.29；P = 0.013），并对12个月的MACE（曲线下面积（AUC） = 0.72，95%置信区间：0.65 - 0.80）和全因死亡率（AUC = 0.74，95%置信区间：0.65 - 0.83）显示出中等预测价值。在来自STEMI患者罪犯冠状动脉的血栓组织浸润巨噬细胞中KAT1表达上调。在梗死周边心肌内的巨噬细胞中也观察到KAT1上调。KYNA水平可能与急性心肌梗死的潜在状态相对应，是预测STEMI进展的一个有前景的生物标志物。
