Serum Metabolomic Analysis of Coronary Heart Disease Patients with Stable Angina Pectoris Subtyped by Traditional Chinese Medicine Diagnostics Reveals Biomarkers Relevant to Personalized Treatments

Figures

• 

  FIGURE 1. Typical base peak intensity (BPI) chromatograms for serum samples obtained in ESI positive (A–C) and negative (D–F) modes based on UPLC/TOF-MS: control group (A, D), Shi group (B, E), and Xu group (C, F).

• 

  FIGURE 2. PLS-DA score plots showing control samples (red dots, n = 30), Shi-subtype samples (blue dots, n = 30) and Xu-subtype samples (green dots, n = 30) in ESI positive (A) and ESI negative modes (B).

• 

  FIGURE 3. Metabolites whose levels were significantly different between groups were organized into a heat map, with red and blue corresponding to increased and decreased levels, respectively. There are seven metabolites, i.e., Linolenic acid, Citric acid, Uric acid, Taurocholic acid, Hypoxanthine, Arachidonic acid, and Glycocholic acid coming from the data set of unbiased analysis using UPLC-qTOF-MS, the nontargeted metabolomics study. There were eight metabolites, i.e., Histidine, Cysteine, Glutamine, LPC (20:2), Cer (d18:1/20:0), Cer (d18:2/22:0), Cer (d18:1/25:0), and SM (d20:0/22:6) coming from the data set of the targeted metabolomics study using QqQ-MS.

• 

  FIGURE 4. Metabolomics pathway analysis indicating select metabolic pathways that are significantly affected in the Shi (A) and Xu (B) subtypes of CHI). p values are shown on the Y-axis, and pathway impact values are shown on the X-axis. The nodes are coloured based on p-value, while node sizes indicate impact values.

• 

  FIGURE 5. Network showing the interactions among indexes related to vascular endothelial damage, ATP, protein targets, metabolic pathways that arc significantly altcrcd in CHD, and the identified metabolites. Grey nodes represent the identified metabolites; red nodes represent pathways related to these metabolites; pink and grccn nodes represent the identified protein targets; bluc nodes rcprcscnt thc relatcd indcxcs of vascular cndothclial damagc and ATP.

• 

  FIGURE 6. Networks of potential serum biomarkers of CHD that varied among the healthy control, Shi-subtype, and Xu-subtype groups. Arrows (“↑↓”) indicated the significantly upregulated or downregulated metabolites in the Shi (red) and Xu (green) patients compared to the healthy control, respectively. The significant changes of metabolites in the Shi group compared to the Xu group are also indicated (blue). There are seven metabolites, i.e., Linolenic acid, Citric acid, Uric acid, Taurocholic acid, Hypoxanthine, Arachidonic acid, and Glycocholic acid coming from the data set of unbiased analysis using UPLC-qTOF-MS, the non-targeted metabolomics study. There were eight metabolites, i.e., Histidine, Cysteine, Glutamine, LPC (20:2), Cer (d18:1/20:0), Cer (d18:1/22:0), Cer (d18:1/25:0), and SM (d22:0/22:6) coming from the data set of the targeted metabolomics study using QqQ-MS.