Untargeted metabolomics identified kynurenine as a predictive prognostic biomarker in acute myocardial infarction - Zhang, Xiaolin; Cai, Yi; Su, Xu; Jing, Quanmin; Liu, Haiwei; Na, Kun; Qiu, Miaohan; Tian, Xiaoxiang; Liu, Dan; Wu, Tianxiao; Yan, Chenghui; Han, Yaling (Frontiers in Immunology, 2022)
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. Coronary artery thrombus and atherosclerotic plaque were analyzed using immunohistochemistry and immunofluorescence. 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 4th quartile 7.12(5.71-10.82) was significantly higher than that in the 3rd quartile 3.03(2.62-3.74), 2nd quartile 1.86(1.70-2.03), and 1st 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 the atherosclerotic coronary artery plaques and thrombi from STEMI patients. Furthermore, IDO1 was mainly expressed in macrophage cells 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.