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. 2025 Jul 17:2025:9123654.
doi: 10.1155/cdr/9123654. eCollection 2025.

Kynurenic Acid Is a Predictive Prognostic Metabolic Marker in ST-Elevation Myocardial Infarction

Affiliations

Kynurenic Acid Is a Predictive Prognostic Metabolic Marker in ST-Elevation Myocardial Infarction

Xiaolin Zhang et al. Cardiovasc Ther. .

Abstract

Background: 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. Objectives: This study evaluated the prognostic value of KYNA, a metabolite of the tryptophan pathway, in STEMI patients. Methods: Untargeted metabolomics by 1H-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. Results: Fifteen differential metabolites were identified between STEMI patients and control subjects by 1H-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; p = 0.0012) and all-cause mortality (HR: 7.11, 95% CI: 1.52-33.29; p = 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. Conclusions: The KYNA level may correspond to the underlying status of acute myocardial infarction and is a promising biomarker for predicting STEMI progression.

Keywords: NMR; ST-acute myocardial infarction; kynurenic acid; metabolic marker; prognostic.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
KYNA levels between the STEMI patients and control subjects.
Figure 2
Figure 2
Kaplan–Meier curves for the 12-month major adverse cardiac event across tertiles of KYNA. MACE denotes a major adverse cardiac event, a composite of all-cause mortality, myocardial infarction, and heart failure.
Figure 3
Figure 3
Restricted cubic spline regression analysis of KYNA for a 12-month major adverse cardiac event. HR, hazard ratio; CI, confidence interval.
Figure 4
Figure 4
Receiver operating characteristic curves and sensitivity analysis of the associations between KYNA and major adverse cardiac events. (a) Receiver operating characteristic curves of KYNA for major adverse cardiac events and all-cause mortality. (b) Sensitivity analysis of the associations between KYNA and major adverse cardiac events.
Figure 5
Figure 5
High KAT1 expression in the thrombi of coronary arteries. Coronary artery thrombi were obtained from patients with STEMI who presented to the cardiac catheterization laboratory. (a) Representative immunofluorescence staining for CD68 and KAT1 in coronary artery thrombi of patients with STEMI. Representative images show the hematoxylin and eosin (HE) and Masson's trichrome staining. (b) Merged immunofluorescence image showing CD68-positive (red) macrophages and KAT1 (green) expression. Nuclei are counterstained with DAPI. The colocalization of KAT1 and CD68-positive macrophages is depicted in the overlay. The square indicates the macrophage cells expressing KAT1.
Figure 6
Figure 6
Representative western blots of KAT1 expression in PBMCs of STEMI patients and control participants. Human PBMCs were obtained from patients with STEMI and control subjects. ⁣p < 0.05 versus control subjects.
Figure 7
Figure 7
KAT1 expression in the mice cardiac tissue remodeling after MI. (a) HE, Masson's trichrome, and Sirius Red staining show that MI is induced by permanently ligating the left anterior descending coronary artery. Cardiac remodeling is assessed at 1, 3, 7, 14, and 28 days post-MI or following sham surgery without ligation. Immunofluorescence analysis reveals that KAT1 expression varies in the infarcted and noninfarcted regions at different time points after MI, with significant upregulation observed 1–3 days post-MI. (b) The KAT1 level is quantitatively assessed at various time following MI through the application of western blot analysis, n = 3. (c) KAT1 expression in the border zone and noninfarct areas after MI. The expression of KAT1 in both the border zone and noninfarcted regions after MI exhibited a statistically significant increase when compared to the sham group, n = 3.

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