Abstract
The detection of left main coronary artery disease (LMCAD) is crucial before ST-segment elevated myocardial infarction (STEMI) or sudden cardiac death. The aim of this study was to identify characteristic metabolite modifications in the LMCAD phenotype, using the metabolomics technique. Metabolic profiles were generated based on ultra-performance liquid chromatography and mass spectrometry, combined with multivariate statistical analysis. Plasma samples were collected prospectively from a propensity-score matched cohort including 44 STEMI patients (22 consecutive LMCAD and 22 non-LMCAD), and 22 healthy controls. A comprehensive metabolomics data analysis was performed with Metaboanalyst 3.0 version. The retinol metabolism pathway was shown to have the strongest discriminative power for the LMCAD phenotype. According to biomarker analysis through receiver-operating characteristic curves, 9-cis-retinoic acid (9cRA) dominated the first page of biomarkers, with area under the curve (AUC) value 0.888. Next highest were a biomarker panel consisting of 9cRA, dehydrophytosphingosine, 1H-Indole-3-carboxaldehyde, and another seven variants of lysophosphatidylcholines, exhibiting the highest AUC (0.933). These novel data propose that the retinol metabolism pathway was the strongest differential pathway for the LMCAD phenotype. 9cRA was the most critical biomarker of LMCAD, and a ten-metabolite plasma biomarker panel, in which 9cRA remained the weightiest, may help develop a potent predictive model for LMCAD in clinic.
Highlights
Chromatography and mass spectrometry (UPLC/Mass spectrometry (MS)) assist diagnosis of a disease or may help monitor its progression, all from a body fluid sample
In a previous study, using UPLC/MS, we showed that sphingolipid metabolism was the most altered pathway in young ST-elevated myocardial infarction (STEMI) patients, and may represent a valuable prognostic factor or potential therapeutic target[12]
462 STEMI patients were recruited. 227 patients were eligible for the study, including twenty-two left main coronary artery disease (LMCAD) and 205 non-LMCAD patients
Summary
Chromatography and mass spectrometry (UPLC/MS) assist diagnosis of a disease or may help monitor its progression, all from a body fluid sample. The technology promotes a more comprehensive, real-time understanding of disease evolution[11]. In a previous study, using UPLC/MS, we showed that sphingolipid metabolism was the most altered pathway in young ST-elevated myocardial infarction (STEMI) patients, and may represent a valuable prognostic factor or potential therapeutic target[12]. To the best of our knowledge, there is a gap in the fund of knowledge that metabolomics can contribute to the study aimed at LMCAD. The aim of this study was to identify plasma characteristic metabolite modifications, and to discover potential biomarkers with good discriminative capability for the LMCAD phenotype. A flow chart illustrating the study design is shown in Supplementary Fig. S1
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