Isobaric tags for relative and absolute quantitation‑based proteomics reveals potential novel biomarkers for the early diagnosis of acute myocardial infarction within 3 h

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 biomark...

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Veröffentlicht in:International journal of molecular medicine 2019-05, Vol.43 (5), p.1991-2004
Hauptverfasser: Du, Changqing, Weng, Yingzheng, Lou, Jiangjie, Zeng, Guangzhong, Liu, Xiaowei, Jin, Hongfeng, Lin, Senna, Tang, Lijiang
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container_end_page 2004
container_issue 5
container_start_page 1991
container_title International journal of molecular medicine
container_volume 43
creator Du, Changqing
Weng, Yingzheng
Lou, Jiangjie
Zeng, Guangzhong
Liu, Xiaowei
Jin, Hongfeng
Lin, Senna
Tang, Lijiang
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
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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&lt;0.01), which was consistent with the ITRAQ results, whereas the expression of fibrinogen γ chain increased at 2 and 3 h (P&lt;0.01) and the expression of integrator complex subunit 4 increased at all three time points (P&lt;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.</description><identifier>ISSN: 1107-3756</identifier><identifier>EISSN: 1791-244X</identifier><identifier>DOI: 10.3892/ijmm.2019.4137</identifier><identifier>PMID: 30896787</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Animals ; Biological markers ; Biomarkers ; Biomarkers - blood ; Cardiomyocytes ; Cardiovascular diseases ; Chromatography ; Cluster Analysis ; Computational biology ; Coronary Angiography ; Cytochrome c ; Cytochrome oxidase ; Diagnosis ; Dogs ; Female ; Fibrin ; Fibrinogen ; Gene Ontology ; Heart attack ; Heart attacks ; Isotope Labeling - methods ; Liquid chromatography ; Male ; Mass spectrometry ; Medical imaging ; Myocardial Infarction - blood ; Myocardial Infarction - diagnosis ; Myocardial Infarction - diagnostic imaging ; Novels ; Oxidases ; Peptides ; Polyethylene ; Protein Interaction Maps ; Protein-protein interactions ; Proteins ; Proteomics ; Proteomics - methods ; Reproducibility of Results ; Scientific imaging ; Spectroscopy ; Surgery ; Technology ; Thrombin ; Time Factors</subject><ispartof>International journal of molecular medicine, 2019-05, Vol.43 (5), p.1991-2004</ispartof><rights>COPYRIGHT 2019 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2019</rights><rights>Copyright: © Du et al. 2019</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-81f24eac6c31f76a0cac0a54a77bbb8b841133e4c62ab382e86890f299f5090c3</citedby><cites>FETCH-LOGICAL-c485t-81f24eac6c31f76a0cac0a54a77bbb8b841133e4c62ab382e86890f299f5090c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30896787$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Du, Changqing</creatorcontrib><creatorcontrib>Weng, Yingzheng</creatorcontrib><creatorcontrib>Lou, Jiangjie</creatorcontrib><creatorcontrib>Zeng, Guangzhong</creatorcontrib><creatorcontrib>Liu, Xiaowei</creatorcontrib><creatorcontrib>Jin, Hongfeng</creatorcontrib><creatorcontrib>Lin, Senna</creatorcontrib><creatorcontrib>Tang, Lijiang</creatorcontrib><title>Isobaric tags for relative and absolute quantitation‑based proteomics reveals potential novel biomarkers for the early diagnosis of acute myocardial infarction within 3 h</title><title>International journal of molecular medicine</title><addtitle>Int J Mol Med</addtitle><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&lt;0.01), which was consistent with the ITRAQ results, whereas the expression of fibrinogen γ chain increased at 2 and 3 h (P&lt;0.01) and the expression of integrator complex subunit 4 increased at all three time points (P&lt;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. 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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. 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The western blot analysis demonstrated that the expression of ATP5B decreased significantly at all three time points (P&lt;0.01), which was consistent with the ITRAQ results, whereas the expression of fibrinogen γ chain increased at 2 and 3 h (P&lt;0.01) and the expression of integrator complex subunit 4 increased at all three time points (P&lt;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.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>30896787</pmid><doi>10.3892/ijmm.2019.4137</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record>
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source Spandidos Publications Journals; MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects Animals
Biological markers
Biomarkers
Biomarkers - blood
Cardiomyocytes
Cardiovascular diseases
Chromatography
Cluster Analysis
Computational biology
Coronary Angiography
Cytochrome c
Cytochrome oxidase
Diagnosis
Dogs
Female
Fibrin
Fibrinogen
Gene Ontology
Heart attack
Heart attacks
Isotope Labeling - methods
Liquid chromatography
Male
Mass spectrometry
Medical imaging
Myocardial Infarction - blood
Myocardial Infarction - diagnosis
Myocardial Infarction - diagnostic imaging
Novels
Oxidases
Peptides
Polyethylene
Protein Interaction Maps
Protein-protein interactions
Proteins
Proteomics
Proteomics - methods
Reproducibility of Results
Scientific imaging
Spectroscopy
Surgery
Technology
Thrombin
Time Factors
title Isobaric tags for relative and absolute quantitation‑based proteomics reveals potential novel biomarkers for the early diagnosis of acute myocardial infarction within 3 h
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