Metabolomics Analysis Identifies Differential Metabolites as Biomarkers for Acute Myocardial Infarction
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Population
2.2. Samples Collection
2.3. Metabolomics Analysis
2.3.1. Identification of Differential Metabolites (DMs)
2.3.2. Validation of DMs
2.3.3. Bioinformatics Analysis
2.4. Statistical Analysis
3. Results
3.1. Baseline Characteristics of Patients
3.2. Untargeted Metabolomics Profiling of Plasma from Discovery Phase
3.2.1. Screening of DMs
3.2.2. Cluster Analysis and Correlation Analysis of DMs
3.2.3. Metabolic Pathway Enrichment Analysis of DMs
3.3. Target Metabolomics Analysis Revealed the Potential Biomarkers of STEMI and NSTEMI Patients in the Validation Phase
3.4. The Correlation between the DMs and CKMB
3.5. The Correlation between the DMs and the Severity of MI
3.6. The Correlation between the DMs and Risk Factors
4. Discussion
4.1. L-Acetylcarnitine, Decanoylcarnitine (C10), Lauroylcarnitine (C12), and Myristoylcarnitine (C14)
4.2. L-aspartic Acid, D-aspartate, cis-4-hydroxy-D-proline, and Itaconic Acid
4.3. Long Chain Monounsaturated Fatty Acids (Palmitoleic Acid/Palmitelaidic Acid)
4.4. Acetylglycine
4.5. Hydroxyphenyllactic Acid (HPLA)
4.6. Arachidonic Acid (AA)
4.7. Study Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Control | STEMI | NSTEMI | UA | p | |
---|---|---|---|---|---|
(n = 18) | (n = 18) | (n = 18) | (n = 12) | ||
Age, median (IQR) | 64.00 (55.75–69.25) | 67.00 (58.00–70.50) | 66.50 (60.00–72.00) | 63.50 (54.75–69.25) | 0.728 |
Male, n (%) | 9 (50%) | 9 (50%) | 9 (50%) | 6 (50%) | 1.000 |
BMI, kg/m2, median (IQR) | 24.49 (23.43–25.55) | 25.24 (21.17–28.04) | 25.71 (22.63–27.89) | 26.30 (23.89–29.84) | 0.312 |
Risk factors, n (%) | |||||
Hypertension, n (%) | 11 (61.1%) | 12 (66.7%) | 11 (61.1%) | 6 (50.0%) | 0.839 |
Diabetes, n (%) | 1 (5.6%) | 7 (38.9%) | 9 (50.0%) | 5 (41.7%) | 0.020 |
Dyslipidemia, n (%) | 2 (11.1%) | 8 (44.4%) | 5 (27.8%) | 5 (41.7%) | 0.112 |
Current smoker, n (%) | 4 (22.2%) | 6 (33.3%) | 4 (22.2%) | 3 (25.0%) | 0.878 |
Cardiac Biomarkers, median (IQR) | |||||
Myo (ng/mL) | NA | 333.00 (190.00–500.00) | 213.50 (123.25–408.50) | 74.20 (62.60–86.55) | <0.001 |
CKMB (ng/mL) | NA | 4.50 (2.85–26.22) | 6.25 (2.50–8.55) | 1.25 (1.00–1.68) | 0.001 |
hs-cTnI (ng/mL) | NA | 0.145 (0.055–1.308) | 0.425 (0.180–0.958) | 0.050 (0.050–0.050) | 0.002 |
BNP (pg/mL) | NA | 30.15 (21.00–48.58) | 57.75 (44.62–221.75) | 32.40 (8.50–95.00) | 0.062 |
D-Dimer (ng/mL) | NA | 124.5 (100.0–409.2) | 164.5 (100.0–545.5) | 134.5 (100.0–224.0) | 0.608 |
Vessel lesion, n (%) | |||||
Single-vessel disease | 0 (0%) | 1 (5.6%) | 8 (44.4%) | 2 (16.7%) | 0.020 |
Multi-vessel disease | 0 (0%) | 17 (94.4%) | 10 (55.6%) | 10 (83.3%) | 0.020 |
Laboratory data | |||||
Blood glucose (mmol/L) | 5.25 (5.10–5.68) | 8.05 (6.70–10.18) | 7.35 (6.32–9.48) | 7.25 (5.88–7.92) | <0.001 |
ALT (U/L) | 16.50 (13.25–30.25) | 34.50 (29.00–80.25) | 17.50 (13.00–24.50) | 16.50 (10.00–20.00) | <0.001 |
AST (U/L) | 17.00 (16.00–23.25) | 114.00 (72.50–349.00) | 31.00 (24.50–58.00) | 18.00 (14.50–19.50) | <0.001 |
AST/ALT | 1.10 (0.80–1.20) | 3.45 (3.05–4.60) | 2.15 (1.30–3.60) | 1.05 (0.90–1.35) | <0.001 |
GGT (U/L) | 22.50 (13.25–51.50) | 20.50 (16.00–30.50) | 21.00 (17.00–31.00) | 25.50 (20.7–32.50) | 0.824 |
TP (g/L) | 68.50 (67.00–71.50) | 64.00 (60.00–67.75) | 64.00 (62.25–67.25) | 63.00 (62.00–64.25) | 0.022 |
TBIL (μmol/L) | 9.15 (7.02–14.48) | 12.40 (10.52–20.72) | 9.55 (8.42–12.15) | 10.10 (6.05–13.42) | 0.094 |
ALP (U/L) | 78.50 (66.00–87.50) | 72.00 (66.00–91.00) | 70.00 (62.50–95.25) | 66.50 (63.25–81.75) | 0.741 |
Urea (mmol/L) | 6.00 (4.90–7.05) | 5.55 (4.98–6.32) | 7.00 (5.70–7.70) | 5.80 (4.90–7.30) | 0.138 |
Uric acid (μmol/L) | 299.50 (255.00–326.25) | 323.00 (249.25–355.75) | 285.00 (246.25–379.75) | 296.00 (252.00–381.50) | 0.982 |
CREA (μmol/L) | 57.50 (50.75–65.75) | 61.00 (48.00–76.00) | 58.00 (50.25–94.25) | 63.00 (60.25–67.25) | 0.866 |
Total cholesterol (mmol/L) | 4.70 (4.08–5.00) | 4.90 (4.18–5.65) | 4.30 (3.50–5.10) | 4.15 (3.80–4.80) | 0.080 |
TG (mmol/L) | 1.16 (0.94–1.40) | 1.28 (1.16–1.87) | 1.61 (1.06–2.44) | 1.91 (1.54–2.18) | 0.032 |
HDL-C (mmol/L) | 1.18 (0.99–1.39) | 1.11 (1.01–1.17) | 0.92 (0.70–1.08) | 0.88 (0.80–0.94) | 0.001 |
LDL-C (mmol/L) | 2.98 (2.60–3.25) | 3.10 (2.72–3.80) | 2.86 (2.06–3.52) | 2.47 (2.21–3.10) | 0.111 |
PLT (×109/L) | 223.00 (209.00–272.50) | 244.00 (206.25–270.00) | 224.50 (198.00–250.25) | 243.00 (203.00–261.50) | 0.733 |
Length of stay (days) | 1.00 (1.00–2.00) | 8.00 (6.25–9.75) | 7.00 (6.00–8.00) | 3.00 (2.75–6.50) | <0.001 |
Group | HMDB ID | Name | Discovery Group | Validation Group | ||||
---|---|---|---|---|---|---|---|---|
FC | p Value | VIP | FC | p Value | VIP | |||
CONTROL-STEMI | HMDB0000191 | L-Aspartic acid | 2.11358712 | 8.21 × 10−7 | 1.577611655 | 3.279994663 | 7.22 × 10−6 | 1.896413607 |
HMDB0000201 | L-Acetylcarnitine | 1.965571929 | 5.54 × 10−5 | 1.340201316 | 1.997169295 | 0.013503462 | 1.253073946 | |
HMDB0000532 | Acetylglycine | 1.725948017 | 0.002633113 | 1.245356672 | 1.733124121 | 0.013522338 | 1.431596275 | |
HMDB0000651 | Decanoylcarnitine | 4.27951669 | 0.000127514 | 1.844505879 | 2.213434982 | 0.013596305 | 1.628532799 | |
HMDB0000755 | Hydroxyphenyllactic acid | 2.714464103 | 1.94 × 10−6 | 1.813677974 | 1.752930832 | 0.049981208 | 1.281225837 | |
HMDB0000954 | Ferulic acid | 6.08440531 | 0.024210222 | 1.290022785 | 1.699855439 | 0.019853603 | 1.375369857 | |
HMDB0002092 | Itaconic acid | 1.598398693 | 2.34 × 10−5 | 1.168632741 | 1.407598002 | 0.000256761 | 1.869606847 | |
HMDB0002250 | Lauroylcarnitine | 2.749056744 | 0.000898345 | 1.466835554 | 2.565912117 | 0.004524507 | 1.522012879 | |
HMDB0005066 | Myristoylcarnitine | 2.166262401 | 2.10 × 10−6 | 1.516728633 | 2.413711584 | 0.002971447 | 1.533423213 | |
HMDB0060460 | cis-4-Hydroxy-D-proline | 1.86876251 | 4.64 × 10−6 | 1.416576047 | 1.553709509 | 0.023058005 | 1.359347074 | |
CONTROL-NSTEMI | HMDB0000191 | L-Aspartic acid | 1.989941591 | 4.99 × 10−6 | 1.411097512 | 2.540095524 | 2.64 × 10−5 | 2.282586177 |
HMDB0001043 | Arachidonic acid | 0.409790387 | 0.000367677 | 1.480786535 | 0.465412831 | 0.034645824 | 1.677437241 | |
HMDB0003229 | Palmitoleic acid | 0.407686414 | 0.002118188 | 1.451292166 | 0.382412824 | 0.01157985 | 1.670575527 | |
HMDB0006483 | D-Aspartic acid | 1.532946834 | 6.03 × 10−5 | 1.053107988 | 2.024616281 | 0.003515567 | 2.032273973 | |
HMDB0012328 | Palmitelaidic acid | 0.557037574 | 0.001707426 | 1.109067827 | 0.476871871 | 0.01046257 | 1.749465707 |
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Zhou, J.; Hou, H.-T.; Song, Y.; Zhou, X.-L.; Chen, H.-X.; Zhang, L.-L.; Xue, H.-M.; Yang, Q.; He, G.-W. Metabolomics Analysis Identifies Differential Metabolites as Biomarkers for Acute Myocardial Infarction. Biomolecules 2024, 14, 532. https://doi.org/10.3390/biom14050532
Zhou J, Hou H-T, Song Y, Zhou X-L, Chen H-X, Zhang L-L, Xue H-M, Yang Q, He G-W. Metabolomics Analysis Identifies Differential Metabolites as Biomarkers for Acute Myocardial Infarction. Biomolecules. 2024; 14(5):532. https://doi.org/10.3390/biom14050532
Chicago/Turabian StyleZhou, Jie, Hai-Tao Hou, Yu Song, Xiao-Lin Zhou, Huan-Xin Chen, Li-Li Zhang, Hong-Mei Xue, Qin Yang, and Guo-Wei He. 2024. "Metabolomics Analysis Identifies Differential Metabolites as Biomarkers for Acute Myocardial Infarction" Biomolecules 14, no. 5: 532. https://doi.org/10.3390/biom14050532