A Non-Targeted Liquid Chromatographic-Mass Spectrometric Metabolomics Approach for Association with Coronary Artery Disease: An Identification of Biomarkers for Depiction of Underlying Biological Mechanisms

Abstract

BackgroundWe performed non-targeted metabolomics analysis using liquid chromatography-mass spectrometry coupled technique to explore the biological mechanism of coronary artery disease (CAD) events for improved prediction.Material/MethodsWe studied the association of CAD events in 4092 individuals and observed the replication of sphingomyelin (28:1), lysophosphatidylcholine (18:2), lysophosphatidylcholine (18:1), and monoglyceride (18:2), which were independent of main CAD risk factors.ResultsWe found that these 4 metabolites were responsible for traditional risk factors and also contributed to the modifications related to reclassification and discrimination. Monoglycerides (MonoGs) were positively associated with C-reactive proteins and body mass index, while lysophosphatidylcholines (LPPCs), which had less evidence of subclinical CAD in an additional 1010 participants, yielded a reverse pattern. An association between monoGs and CAD independence of triglycerides (triGs) were also observed. On the basis of Mendelian randomization analysis, we observed a positive but weak irregular effect (odds ratio per unit increase in standard deviation in monoG=1.11, P-value=0.05) on CAD.ConclusionsOur work establishes the relationship of metabolome with coronary artery disease and explains the biological mechanism of CAD events, as we identified the above-mentioned metabolites along with the evidence supporting their clinical use.

Targeted Metabolomics Shows Low Plasma Lysophosphatidylcholine 18:2 Predicts Greater Decline of Gait Speed in Older Adults: The Baltimore Longitudinal Study of Aging

“…In a non-targeted metabolomics study involving more than 3,600 adults from three population-based studies, independent of cardiovascular risk factors, circulating LPC 18:2 predicted incident coronary heart disease (Hazards Ratio 0:81 per standard deviation, p < .001) (51). In a non-targeted metabolomics study of 4,092 adults, LPC 18:2 was an independent predictor of incident coronary artery disease (52). In three independent prospective cohort studies [KORA S4, KORA S2, and the Age, Gene/Environment Susceptibility Reykjavik -Risk Evaluation for Infarct Estimates (AGES-REFINE) studies], three metabolites (LPC 18:2, LPC 17:0, and arginine) improved the predictive value of the Framingham risk score for myocardial infarction (53).…”

Identification and Validation of Plasma Metabolomics Reveal Potential Biomarkers for Coronary Heart Disease

“…Within the intestinal wall, MGs are involved in the resynthesis of diglycerides and triglycerides through the monoacylglycerol pathway, followed by lymph transportation. 35) MGs are, therefore, central to the synthesis and breakdown of triglycerides, and a positive causal effect of plasma triglyceride levels on CHD risk has recently been shown in a large randomized analysis. 36) Moreover, single-nucleotide polymorphisms of MG genes have been associated with CHD, even after adjustment for main cardiovascular risk factors.…”

Metabolomics Study of the Biochemical Changes in the Plasma of Myocardial Infarction Patients

“…The degradation of glycerophospholipids by phospholipase A2 generates LPC and AA. LPC is then enzymatically converted to LPA ( Wymann and Schneiter, 2008 ) and has been identified as risk factor biomarkers for coronary artery disease ( Zhang et al, 2017 ). Moreover, increased AA (No.…”