Dataset Information

Screening and identification of potential protein biomarkers for the early diagnosis of acute myocardial infarction.

ABSTRACT:

Background

Acute 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.

Methods

Serum 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.

Results

A 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.

Conclusions

In 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.

SUBMITTER: Shi LY

PROVIDER: S-EPMC8246203 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

Project description:Acute myocardial infarction (AMI) is a common cause of death in numerous countries. Understanding the molecular mechanisms of the disease and analyzing potential biomarkers of AMI is crucial. However, specific diagnostic biomarkers have thus far not been fully established and candidate regulatory targets for AMI remain to be determined. In the present study, the AMI gene chip dataset GSE48060 comprising blood samples from control subjects with normal cardiac function (n=21) and patients with AMI (n=26) was downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) between the AMI and control groups were identified with the online tool GEO2R. The co-expression network of DEGs was analyzed by calculating the Pearson correlation coefficient of all gene pairs, mutual rank screening and cutoff threshold screening. Subsequently, the Gene Ontology (GO) database was used to analyze the genes' functions and pathway enrichment of genes in the most important modules was performed. Kyoto Encyclopedia of Genes and Genomes (KEGG) Disease and BioCyc were used to analyze the hub genes in the module to determine important sub-pathways. In addition, the expression of hub genes was confirmed by reverse transcription-quantitative PCR in AMI and control specimens. In the present study, 52 DEGs, including 26 upregulated and 26 downregulated genes, were identified. As key hub genes, three upregulated genes (AKR1C3, RPS24 and P2RY12) and three downregulated genes (ACSL1, B3GNT5 and MGAM) were identified from the co-expression network. Furthermore, GO enrichment analysis of all AMI co-expression network genes revealed functional enrichment mainly in 'RAGE receptor binding' and 'negative regulation of T cell cytokine production'. In addition, KEGG Disease and BioCyc analysis indicated functional enrichment of the genes RPS24 and P2RY12 in 'cardiovascular diseases', of AKR1C3 in 'cardenolide biosynthesis', of MGAM in 'glycogenolysis', of B3GNT5 in 'glycosphingolipid biosynthesis' and of ACSL1 in 'icosapentaenoate biosynthesis II'. In conclusion, the hub genes AKR1C3, RPS24, P2RY12, ACSL1, B3GNT5 and MGAM are potential markers of AMI, and have potential application value in the diagnosis of AMI.