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A Comparative Metabolomics Approach Reveals Early Biomarkers for Metabolic Response to Acute Myocardial Infarction.

ABSTRACT: Discovery of novel biomarkers is critical for early diagnosis of acute coronary syndrome (ACS). Serum metabolite profiling of ST-elevation myocardial infarction (STEMI), unstable angina (UA) and healthy controls was performed using gas chromatography mass spectrometry (GC/MS), solid-phase microextraction coupled to gas chromatography mass spectrometry (SPME-GC/MS) and nuclear magnetic resonance (¹H-NMR). Multivariate data analysis revealed a metabolic signature that could robustly discriminate STEMI patients from both healthy controls and UA patients. This panel of biomarkers consisted of 19 metabolites identified in the serum of STEMI patients. One of the most intriguing biomarkers among these metabolites is hydrogen sulfide (H₂S), an endogenous gasotransmitter with profound effect on the heart. Serum H₂S absolute levels were further investigated using a quantitative double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). This highly sensitive immunoassay confirmed the elevation of serum H₂S in STEMI patients. H₂S level discriminated between UA and STEMI groups, providing an initial insight into serum-free H₂S bioavailability during ACS. In conclusion, the current study provides a detailed map illustrating the most predominant altered metabolic pathways and the biochemical linkages among the biomarker metabolites identified in STEMI patients. Metabolomics analysis may yield novel predictive biomarkers that will potentially allow for an earlier medical intervention.

SUBMITTER: Ali SE

PROVIDER: S-EPMC5099572 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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A Comparative Metabolomics Approach Reveals Early Biomarkers for Metabolic Response to Acute Myocardial Infarction.

Ali Sara E SE Farag Mohamed A MA Holvoet Paul P Hanafi Rasha S RS Gad Mohamed Z MZ

Scientific reports 20161108

Discovery of novel biomarkers is critical for early diagnosis of acute coronary syndrome (ACS). Serum metabolite profiling of ST-elevation myocardial infarction (STEMI), unstable angina (UA) and healthy controls was performed using gas chromatography mass spectrometry (GC/MS), solid-phase microextraction coupled to gas chromatography mass spectrometry (SPME-GC/MS) and nuclear magnetic resonance (<sup>1</sup>H-NMR). Multivariate data analysis revealed a metabolic signature that could robustly dis ...[more]

PMID: 27821850

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Project description:BackgroundAcute myocardial infarction (AMI) is the most serious type of heart disease. Clinically, there is an urgent need to discover diagnostic biomarkers for the early diagnosis of AMI.MethodsSerum proteomic profiles in AMI patients, healthy controls, and stable angina pectoris (SAP) patients were explored and compared by iTRAQ-2DLC-MS/MS. The clinical data of AMI patients were also analyzed. Differentially expressed proteins were validated by enzyme linked immunosorbent assay (ELISA), and diagnostic models were constructed.ResultsA total of 39 differentially expressed proteins were identified in AMI patients. The results showed that the serum levels of apolipoprotein E (APOE) in AMI patients were notably higher than those in the healthy controls (P=0.0172). The serum levels of aspartate aminotransferase (AATC) in AMI patients were markedly higher than those in the healthy controls and SAP patients (P<0.0001 and P<0.0001, respectively). The serum levels of fibronectin (FINC) in SAP patients were significantly higher than those in the healthy controls and AMI patients (P=0.0043 and P=0.0044, respectively). Clinical data analysis showed a considerable difference in blood glucose levels, troponin I (TNI), and creatine kinase (CK) in AMI patients compared with SAP patients and healthy controls. A diagnostic model consisting of AATC and clinical indicators [lactate dehydrogenase (LDH) and CK] was established to distinguish between AMI patients and healthy controls, with an area under the curve (AUC) value of 0.993 sensitivity and specificity of 96.2% and 96.3%, respectively. A diagnostic model consisting of AATC and CK was established to distinguish between AMI patients and SAP patients, with an AUC value of 0.975 and a sensitivity and specificity of 85.2% and 79.30%, respectively.ConclusionsIn this study, differentially expressed proteins in AMI patients were combined with clinical indexes, LDH and CK, and two diagnostic models were constructed. This study may provide meaningful data for the early diagnosis of AMI.

Project description:Acute myocardial infarction (AMI) is one of the most common and life‑threatening cardiovascular diseases. However, the ability to diagnose AMI within 3 h is currently lacking. The present study aimed to identify the differentially expressed proteins of AMI within 3 h and to investigate novel biomarkers using isobaric tags for relative and absolute quantitation (ITRAQ) technology. A total of 30 beagle dogs were used for establishing the MI models successfully by injecting thrombin powder and a polyethylene microsphere suspension. Serum samples were collected prior to (0 h) and following MI (1, 2 and 3 h). ITRAQ‑coupled liquid chromatography‑mass spectrometry (LC‑MS) technology was used to identify the differentially expressed proteins. The bioinformatics analysis selected several key proteins in the initiation of MI. Further analysis was performed using STRING software. Finally, western blot analysis was used to evaluate the results obtained from ITRAQ. In total, 28 proteins were upregulated and 23 were downregulated in the 1 h/0 h group, 28 proteins were upregulated and 26 were downregulated in the 2 h/0 h group, and 24 proteins were upregulated and 19 were downregulated in the 3 h/0 h group. The Gene Ontology (GO) annotation and functional enrichment analysis identified 19 key proteins. Protein‑protein interactions (PPIs) were investigated using the STRING database. GO enrichment analysis revealed that a number of key proteins, including ATP synthase F1 subunit β (ATP5B), cytochrome c oxidase subunit 2 and cytochrome c, were components of the electron transport chain and were involved in energy metabolism. The western blot analysis demonstrated that the expression of ATP5B decreased significantly at all three time points (P<0.01), which was consistent with the ITRAQ results, whereas the expression of fibrinogen γ chain increased at 2 and 3 h (P<0.01) and the expression of integrator complex subunit 4 increased at all three time points (P<0.01), which differed from the ITRAQ results. According to the proteomics of the beagle dog MI model, ATP5B may serve as the potential biomarkers of AMI. Mitochondrial dysfunction and disruption of the electron transport chain may be critical indicators of early MI within 3 h. These finding may provide a novel direction for the diagnosis of AMI.

Dataset Information

A Comparative Metabolomics Approach Reveals Early Biomarkers for Metabolic Response to Acute Myocardial Infarction.

Publications

A Comparative Metabolomics Approach Reveals Early Biomarkers for Metabolic Response to Acute Myocardial Infarction.

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