| ObjectiveThe tryptophan/kynurenine pathway plays a key role in the increase of cardiovascular disease incidence by regulating inflammation,oxidative stress and immune activation.In this study,we analysed the changes of serum non-targeted metabolomics in patients with ST segment elevation myocardial infarction(STEMI);targeted metabolomics was used to analyze the relationship between the key metabolites of tryptophan/kynurenine pathway in STEMI patients.At the same time we evaluated the predictive value of Kynurenine/Tryptophan(KTR)for the major adverse cardiac and cerebral events(MACCE)in STEMI patients.Methods1.From June 2016 to December 2017,504 subjects with chest pain were admitted to the General Hospital of Northern Theater Command,which met the criteria for admission and discharge,including 224 cases of control group and 280 cases of STEMI group.In order to clarify the characteristics of serum metabolism in the STEMI patients,50 cases were selected from the control group and STEMI group respectively,the metabolites were analyzed by Non-targeted metabonomics using nuclear magnetic resonance(NMR).2.Among the differential metabolites in the serum of STEMI patients,the tryptophan pathway with high specificity and significant P value were selected for targeted metabonomic analysis.Ultraperformance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry(UPLC/Q-TOF)was used to analyze the target metabolomics among the selected subjects,including 224 cases from the STEMI group and 280 cases from the control group.The concentration of tryptophan(Trp)and kynurenines in serum were analyzed.3.According to the level of KTR in serum,we divided the STEMI patients into four groups for prediction and analysis of 1-year MACCE events in the STEMI group.Results1.Non-targeted metabolomics revealed that STEMI patients and control groups had different metabolic characteristics.15 kinds of metabolic markers including tryptophan were related to STEMI,the expression levels were significantly different(P<0.05).Pyroglutamic acid,3-hydroxybutyric acid,α-glucose and salicylic acid were highly expressed in serum of STEMI patients;while glutamic acid,tryptophan,histidine,sorbitol,formate,tyrosine,isoleucine,leucine,valine,glycine,and alanine were underexpressed in serum of STEMI patients.2.Targeted metabolomics results showed that serum concentration of tryptophan in STEMI group were significantly lower than those in the control group(P=0.001);the expression levels of IDO,kynurenine,kynurenic acid,3-hydroxykynurenine were increased in the STEMI group(P<0.05).The serum KTR of STEMI patients was significantly higher than that of the control group(12.8±5.4 vs 27.0±12.1),and the difference was statistically significant(P<0.000).3.The incidence of MACCE in 280 patients with STEMI was 6.4%(17/266)after one-year follow-up.The KTR level of STEMI patients with MACCE events was significantly higher than that those without MACCE events,the difference was statistically significant(40.6±17.0 vs 25.7±11.1,P=0.002).Conclusions1.Non-targeted metabonomic results showed that a total of 15 different metabolic markers were identified in the serum of STEMI patients compared with the control group(P<0.05).2.Targeted metabonomic analysis showed that the serum tryptophan level was significantly decreased in STEMI patients,while the level of IDO,KTR and kynurenines(kynurenine,kynurenic acid,3-hydroxykynurenine,3-hydroxyanthranilic acid and xanthene acid)were significantly increased in STEMI patients.3.The higher the expression level of serum KTR,the higher the risk of MACCE in STEMI patients within one year. |
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