Untargeted metabolomics identified kynurenine as a predictive prognostic biomarker in acute myocardial infarction

Xiaolin Zhang; Yi Cai; Xu Su; Quanmin Jing; Haiwei Liu; Kun Na; Miaohan Qiu; Xiaoxiang Tian; Dan Liu; Tianxiao Wu; Chenghui Yan; Yaling Han

doi:10.3389/fimmu.2022.950441

Untargeted metabolomics identified kynurenine as a predictive prognostic biomarker in acute myocardial infarction

Front Immunol. 2022 Nov 2:13:950441. doi: 10.3389/fimmu.2022.950441. eCollection 2022.

Authors

Xiaolin Zhang^{1

2}, Yi Cai², Xu Su², Quanmin Jing², Haiwei Liu², Kun Na², Miaohan Qiu², Xiaoxiang Tian², Dan Liu², Tianxiao Wu³, Chenghui Yan², Yaling Han^{1

2}

Affiliations

¹ Second Affiliated Hospital of Dalian Medical University, Dalian, China.
² Cardiovascular Research Institute and Department of Cardiology, The General Hospital of Northern Theater Command, Shenyang, China.
³ Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China.

Abstract

Objective: The occurrence of cardiovascular adverse events in the first year after ST-acute myocardial infarction (STEMI) remains high; therefore, identification of patients with poor prognosis is essential for early intervention. This study aimed to evaluate the prognostic value of metabolomics-based biomarkers in STEMI patients and explore their functional mechanisms.

Methods: Metabolite profiling was performed using nuclear magnetic resonance. The plasma concentration of Kynurenine (Kyn) was measured using ultraperformance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry. Major adverse cardiac and cerebral events were assessed for 1 year. A functional metabolomics strategy was proposed for investigating the role of Kyn in both vitro and vivo models.

Results: The adjusted hazard ratios in STEMI patients for Kyn in the 4^th quartile 7.12(5.71-10.82) was significantly higher than that in the 3^rd quartile 3.03(2.62-3.74), 2^nd quartile 1.86(1.70-2.03), and 1^st quartile 1.20(0.93-1.39).The incidence of MACCE was significantly different among Kyn quartiles and the highest incidence of MACCE was observed in the 4th quartile when compared with the 1st quartile (9.84% vs.2.85%, P<0.001).Immunofluorescence staining indicated that indoleamine-pyrrole 2,3-dioxygenase (IDO1) was located in the CD68 positive staining area of thrombi from STEMI patients and Kyn was induced in the early phase after myocardial infarction. Kyn could trigger inflammation and oxidative stress of macrophage cells by activation of the Sirt3-acSOD2/IL-1β signaling pathway in vitro.

Conclusions: Plasma Kyn levels were positively associated with the occurrence of STEMI. Kyn could induce macrophage cells inflammation and oxidative stress by activating the Sirt3-acSOD2/IL-1β pathway following myocardial ischemia injury. Kyn could be a robust biomarker for STEMI prognosis and reduction of Kyn could be beneficial in STEMI patients.

Keywords: Kynurenine; ST-acute myocardial infarction; biomarker; indoleamine-pyrrole 2,3-dioxygenase; metabolites; prognosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Humans
Inflammation / complications
Kynurenine
Metabolomics
Myocardial Infarction* / complications
Prognosis
ST Elevation Myocardial Infarction* / complications
Sirtuin 3*

Substances

Kynurenine
Sirtuin 3
Biomarkers