Comprehensive Plasma Metabolome for Identification of Novel Biomarkers of Acute Myocardial Infarction

Jun Liu , Yi Yu , Qiqi Lu , Shan-Qiang Zhang , Ji-Cheng Li

MedComm ›› 2025, Vol. 6 ›› Issue (8) : e70303

PDF
MedComm ›› 2025, Vol. 6 ›› Issue (8) : e70303 DOI: 10.1002/mco2.70303
ORIGINAL ARTICLE

Comprehensive Plasma Metabolome for Identification of Novel Biomarkers of Acute Myocardial Infarction

Author information +
History +
PDF

Abstract

Metabolic disorders play a crucial role in the occurrence of acute myocardial infarction (AMI). The objective of this research was to elucidate the characteristic metabolic profile of AMI and provide potential biomarkers for AMI. This study employed a targeted metabolomics approach utilizing the Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS) system to identify both hydrophilic and hydrophobic metabolites present in plasma samples. Among 1498 detected metabolites, 78 were the most significantly expressed in the AMI group. Functional synergy analysis showed prominent enrichment in the pathways of steroid hormone biosynthesis, biosynthesis of unsaturated fatty acids, bile secretion, and ABC transporters. The metabolites 2-Hydroxy-6-Aminopurine, 17α-Hydroxyprogesterone, and S-(methyl) glutathione have been identified as potential metabolic biomarkers linked to the pathogenesis of AMI. The diagnostic model that integrates these three metabolites exhibited exceptional performance in both the discovery and validation cohorts, attaining an area under the curve (AUC) value greater than 0.9. In addition, based on the follow-up data, we also found that the three metabolites were potential predictive biomarkers for poor prognosis of AMI. This study delineated the characteristic metabolic profile of AMI and assessed the value of metabolic molecules in the diagnosis and prognosis of AMI. This may provide insights for understanding the AMI occurrence and progression.

Keywords

AMI / diagnosis / metabolomics / prognosis / UPLC-MS/MS

Cite this article

Download citation ▾
Jun Liu, Yi Yu, Qiqi Lu, Shan-Qiang Zhang, Ji-Cheng Li. Comprehensive Plasma Metabolome for Identification of Novel Biomarkers of Acute Myocardial Infarction. MedComm, 2025, 6(8): e70303 DOI:10.1002/mco2.70303

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

G. A. Roth, C. Johnson, A. Abajobir, et al., “Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015,” Journal of the American College of Cardiology 70, no. 1 (2017): 1-25.

[2]

G. W. Reed, J. E. Rossi, and C. P. Cannon, “Acute Myocardial Infarction,” Lancet 389, no. 10065 (2017): 197-210.

[3]

J. Chang, X. Liu, and Y. Sun, “Mortality due to Acute Myocardial Infarction in China From 1987 to 2014: Secular Trends and Age-Period-Cohort Effects,” International Journal of Cardiology 227 (2017): 229-238.

[4]

Q. Zhao, Y. Yang, Z. Chen, H. Yu, and H. Xu, “Changes in Characteristics, Risk Factors, and In-Hospital Mortality Among Patients With Acute Myocardial Infarction in the Capital of China Over 40 years,” International Journal of Cardiology 265 (2018): 30-34.

[5]

H. Thiele, S. de Waha-Thiele, A. Freund, U. Zeymer, S. Desch, and S. Fitzgerald, “Management of Cardiogenic Shock,” EuroIntervention 17, no. 6 (2021): 451-465.

[6]

Y. Chen, Y. Tao, L. Zhang, W. Xu, and X. Zhou, “Diagnostic and Prognostic Value of Biomarkers in Acute Myocardial Infarction,” Postgraduate Medical Journal 95, no. 1122 (2019): 210-216.

[7]

J. Nielsen, “Systems Biology of Metabolism,” Annual Review of Biochemistry 86 (2017): 245-275.

[8]

M. M. Rinschen, J. Ivanisevic, M. Giera, and G. Siuzdak, “Identification of Bioactive Metabolites Using Activity Metabolomics,” Nature Reviews Molecular Cell Biology 20, no. 6 (2019): 353-367.

[9]

A. Khan, Y. Choi, J. H. Back, S. Lee, S. H. Jee, and Y. H. Park, “High-Resolution Metabolomics Study Revealing L-homocysteine Sulfinic Acid, Cysteic Acid, and Carnitine as Novel Biomarkers for High Acute Myocardial Infarction Risk,” Metabolism 104 (2020): 154051.

[10]

J. Y. Park, S. H. Lee, M. J. Shin, and G. S. Hwang, “Alteration in Metabolic Signature and Lipid Metabolism in Patients With Angina Pectoris and Myocardial Infarction,” PLoS One 10, no. 8 (2015): e0135228.

[11]

C. H. Johnson, J. Ivanisevic, and G. Siuzdak, “Metabolomics: Beyond Biomarkers and Towards Mechanisms,” Nature Reviews Molecular Cell Biology 17, no. 7 (2016): 451-9.

[12]

I. J. Choi, S. Lim, E. H. Choo, et al., “Impact of Intravascular Ultrasound on Long-Term Clinical Outcomes in Patients With Acute Myocardial Infarction,” JACC: Cardiovascular Interventions 14, no. 22 (2021): 2431-2443.

[13]

A. P. DeFilippis, A. R. Chapman, N. L. Mills, et al., “Assessment and Treatment of Patients with Type 2 Myocardial Infarction and Acute Nonischemic Myocardial Injury,” Circulation 140, no. 20 (2019): 1661-1678.

[14]

O. P. Trifonova, D. L. Maslov, E. E. Balashova, and P. G. Lokhov, “Mass Spectrometry-Based Metabolomics Diagnostics—Myth or Reality?,” Expert Review of Proteomics 18, no. 1 (2021): 7-12.

[15]

R. Bujak, W. Struck-Lewicka, M. J. Markuszewski, and R. Kaliszan, “Metabolomics for Laboratory Diagnostics,” Journal of Pharmaceutical and Biomedical Analysis 113 (2015): 108-20.

[16]

R. Wang, B. Li, S. M. Lam, and G. Shui, “Integration of Lipidomics and Metabolomics for In-Depth Understanding of Cellular Mechanism and Disease Progression,” Journal of Genetics and Genomics 47, no. 2 (2020): 69-83.

[17]

Y. Fan, Y. Li, Y. Chen, et al., “Comprehensive Metabolomic Characterization of Coronary Artery Diseases,” Journal of the American College of Cardiology 68, no. 12 (2016): 1281-93.

[18]

F. F. Li, N. Liu, W. Liu, et al., “Role of Dihydroceramides in the Progression of Acute-on-Chronic Liver Failure in Rats,” Chinese Medical Journal 133, no. 2 (2020): 198-204.

[19]

M. Guo, X. Fan, G. Tuerhongjiang, et al., “Targeted Metabolomic Analysis of Plasma Fatty Acids in Acute Myocardial Infarction in Young Adults,” Nutrition, Metabolism and Cardiovascular Diseases 31, no. 11 (2021): 3131-3141.

[20]

S. E. Ali, M. A. Farag, P. Holvoet, R. S. Hanafi, and M. Z. Gad. A Comparative Metabolomics Approach Reveals Early Biomarkers for Metabolic Response to Acute Myocardial Infarction. Scientific Reports 6 (2016): 36359.

[21]

C. J. Zuurbier, L. Bertrand, C. R. Beauloye, et al., “Cardiac Metabolism as a Driver and Therapeutic Target of Myocardial Infarction,” Journal of Cellular and Molecular Medicine 24, no. 11 (2020): 5937-5954.

[22]

G. D. Lopaschuk, Q. G. Karwi, R. Tian, A. R. Wende, and E. D. Abel, “Cardiac Energy Metabolism in Heart Failure,” Circulation Research 128, no. 10 (2021): 1487-1513.

[23]

W. Makarewicz, “Response of Purine Metabolism to Hypoxia and Ischemia,” Advances in Experimental Medicine and Biology 431 (1998): 351-7.

[24]

O. Fisher, R. A. Benson, and C. H. Imray, “The Clinical Application of Purine Nucleosides as Biomarkers of Tissue Ischemia and Hypoxia in Humans In Vivo,” Biomarkers in Medicine 13, no. 11 (2019): 953-965.

[25]

K. Fan, W. Huang, H. Qi, et al., “The Egr-1/miR-15a-5p/GPX4 Axis Regulates Ferroptosis in Acute Myocardial Infarction,” European Journal of Pharmacology 909 (2021): 174403.

[26]

M. Gao, P. Monian, N. Quadri, R. Ramasamy, and X. Jiang, “Glutaminolysis and Transferrin Regulate Ferroptosis,” Molecular Cell 59, no. 2 (2015): 298-308.

[27]

B. R. Stockwell, J. P. Friedmann Angeli, and H. Bayir, “Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease,” Cell 171, no. 2 (2017): 273-285.

[28]

K. Hollenstein, R. J. Dawson, and K. P. Locher, “Structure and Mechanism of ABC Transporter Proteins,” Current Opinion in Structural Biology 17, no. 4 (2007): 412-8.

[29]

A. Tawbeh, C. Gondcaille, D. Trompier, and S. Savary, “Peroxisomal ABC Transporters: An Update,” International Journal of Molecular Sciences 22, no. 11 (2021): 6093.

[30]

S. Y. Morita and T. Terada, “Molecular Mechanisms for Biliary Phospholipid and Drug Efflux Mediated by ABCB4 and Bile Salts,” BioMed Research International 2014 (2014): 954781.

[31]

M. Nicolaou, E. J. Andress, J. K. Zolnerciks, P. H. Dixon, C. Williamson, and K. J. Linton, “Canalicular ABC Transporters and Liver Disease,” Journal of Pathology 226, no. 2 (2012): 300-15.

[32]

X. Liu, “ABC Family Transporters,” Advances in Experimental Medicine and Biology 1141 (2019): 13-100.

[33]

Y. Sun, J. Wang, T. Long, et al., “Molecular Basis of Cholesterol Efflux via ABCG Subfamily Transporters,” PNAS 118, no. 34 (2021): e2110483118.

[34]

N. Wang and M. Westerterp, “ABC Transporters, Cholesterol Efflux, and Implications for Cardiovascular Diseases,” Advances in Experimental Medicine and Biology 1276 (2020): 67-83.

[35]

M. Muller, M. Voss, C. Heise, T. Schulz, J. Bunger, and E. Hallier, “High-Performance Liquid Chromatography/Fluorescence Detection of S-Methylglutathione Formed by Glutathione-S-Transferase T1 In Vitro,” Archives of Toxicology 74, no. 12 (2001): 760-7.

[36]

K. P. Cantor, R. Hoover, T. J. Mason, and L. J. McCabe, “Associations of Cancer Mortality With Halomethanes in Drinking Water,” Journal of the National Cancer Institute 61, no. 4 (1978): 979-85.

[37]

F. Yang, J. Zhang, W. Chu, D. Yin, and M. R. Templeton, “Haloactamides Versus Halomethanes Formation and Toxicity in Chloraminated Drinking Water,” Journal of Hazardous Materials 274 (2014): 156-63.

[38]

L. W. Condie, C. L. Smallwood, and R. D. Laurie, “Comparative Renal and Hepatotoxicity of Halomethanes: Bromodichloromethane, Bromoform, Chloroform, Dibromochloromethane and Methylene Chloride,” Drug and Chemical Toxicology 6, no. 6 (1983): 563-78.

[39]

M. F. Mnif, M. Kamoun, F. Mnif, et al., “Metabolic Profile and Cardiovascular Risk Factors in Adult Patients With Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency,” Indian Journal of Endocrinology and Metabolism 16, no. 6 (2012): 939-46.

[40]

L. H. Y. Lau, J. Nano, A. Cecil, et al., “Cross-Sectional and Prospective Relationships of Endogenous Progestogens and Estrogens With Glucose Metabolism in Men and Women: A KORA F4/FF4 Study,” BMJ Open Diabetes Research & Care 9, no. 1 (2021): e001951.

[41]

K. Kino, T. Kawada, M. Hirao-Suzuki, M. Morikawa, and H. Miyazawa, “Products of Oxidative Guanine Damage Form Base Pairs With Guanine,” International Journal of Molecular Sciences 21, no. 20 (2020): 7645.

[42]

W. L. Neeley and J. M. Essigmann, “Mechanisms of Formation, Genotoxicity, and Mutation of Guanine Oxidation Products,” Chemical Research in Toxicology 19, no. 4 (2006): 491-505.

RIGHTS & PERMISSIONS

2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.

AI Summary AI Mindmap
PDF

12

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/