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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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 |
doi_str_mv | 10.3892/ijmm.2019.4137 |
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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<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.</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<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.</description><subject>Animals</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Cardiomyocytes</subject><subject>Cardiovascular diseases</subject><subject>Chromatography</subject><subject>Cluster Analysis</subject><subject>Computational biology</subject><subject>Coronary Angiography</subject><subject>Cytochrome c</subject><subject>Cytochrome oxidase</subject><subject>Diagnosis</subject><subject>Dogs</subject><subject>Female</subject><subject>Fibrin</subject><subject>Fibrinogen</subject><subject>Gene Ontology</subject><subject>Heart attack</subject><subject>Heart attacks</subject><subject>Isotope Labeling - methods</subject><subject>Liquid chromatography</subject><subject>Male</subject><subject>Mass spectrometry</subject><subject>Medical imaging</subject><subject>Myocardial Infarction - blood</subject><subject>Myocardial Infarction - diagnosis</subject><subject>Myocardial Infarction - diagnostic imaging</subject><subject>Novels</subject><subject>Oxidases</subject><subject>Peptides</subject><subject>Polyethylene</subject><subject>Protein Interaction Maps</subject><subject>Protein-protein interactions</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Proteomics - methods</subject><subject>Reproducibility of Results</subject><subject>Scientific imaging</subject><subject>Spectroscopy</subject><subject>Surgery</subject><subject>Technology</subject><subject>Thrombin</subject><subject>Time Factors</subject><issn>1107-3756</issn><issn>1791-244X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptUktuFDEUbCEQCYEtS2SJdQ_-ddveIEURhEiR2IDEznp22zMeutsTu3ui2XEFbpALcAmOwklwKyGAFHlh672qeq-sqqqXBK-YVPRN2A7DimKiVpww8ag6JkKRmnL-5XF5EyxqJpr2qHqW8xZj2nAln1ZHDEvVCimOqx8XORpIwaIJ1hn5mFByPUxh7xCMHQKTYz9PDl3NME5hKp04_vr23UB2HdqlOLk4BJsLa--gz2hXKgUIPRrj3vXIhDhA-urSrfi0cchB6g-oC7AeYw4ZRY_ALjOGQ7SQuoUcRg_JLsPQdZg2YUTs583mefXElyHuxd19Un1-_-7T2Yf68uP5xdnpZW25bKZaEk-5A9taRrxoAVuwGBoOQhhjpJGcEMYcty0FwyR1spUKe6qUb7DClp1Ub291d7MZXGeLowS93qVQvBx0hKD_74xho9dxr1vOGeNNEXh9J5Di1ezypLdxTmPZWVOKVYNbIsRf1Bp6p4vlWMTsELLVp41kShGueEGtHkCV07ny83F0PpT6QwSbYs7J-fvFCdZLavSSGr2kRi-pKYRX_9q9h_-JCfsNwtnEtw</recordid><startdate>20190501</startdate><enddate>20190501</enddate><creator>Du, Changqing</creator><creator>Weng, Yingzheng</creator><creator>Lou, Jiangjie</creator><creator>Zeng, Guangzhong</creator><creator>Liu, Xiaowei</creator><creator>Jin, Hongfeng</creator><creator>Lin, Senna</creator><creator>Tang, Lijiang</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><general>D.A. 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blood</topic><topic>Cardiomyocytes</topic><topic>Cardiovascular diseases</topic><topic>Chromatography</topic><topic>Cluster Analysis</topic><topic>Computational biology</topic><topic>Coronary Angiography</topic><topic>Cytochrome c</topic><topic>Cytochrome oxidase</topic><topic>Diagnosis</topic><topic>Dogs</topic><topic>Female</topic><topic>Fibrin</topic><topic>Fibrinogen</topic><topic>Gene Ontology</topic><topic>Heart attack</topic><topic>Heart attacks</topic><topic>Isotope Labeling - methods</topic><topic>Liquid chromatography</topic><topic>Male</topic><topic>Mass spectrometry</topic><topic>Medical imaging</topic><topic>Myocardial Infarction - blood</topic><topic>Myocardial Infarction - diagnosis</topic><topic>Myocardial Infarction - diagnostic imaging</topic><topic>Novels</topic><topic>Oxidases</topic><topic>Peptides</topic><topic>Polyethylene</topic><topic>Protein Interaction Maps</topic><topic>Protein-protein interactions</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Proteomics - methods</topic><topic>Reproducibility of Results</topic><topic>Scientific imaging</topic><topic>Spectroscopy</topic><topic>Surgery</topic><topic>Technology</topic><topic>Thrombin</topic><topic>Time Factors</topic><toplevel>online_resources</toplevel><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><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Du, Changqing</au><au>Weng, Yingzheng</au><au>Lou, Jiangjie</au><au>Zeng, Guangzhong</au><au>Liu, Xiaowei</au><au>Jin, Hongfeng</au><au>Lin, Senna</au><au>Tang, Lijiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Isobaric tags for relative and absolute quantitation‑based proteomics reveals potential novel biomarkers for the early diagnosis of acute myocardial infarction within 3 h</atitle><jtitle>International journal of molecular medicine</jtitle><addtitle>Int J Mol Med</addtitle><date>2019-05-01</date><risdate>2019</risdate><volume>43</volume><issue>5</issue><spage>1991</spage><epage>2004</epage><pages>1991-2004</pages><issn>1107-3756</issn><eissn>1791-244X</eissn><abstract>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.</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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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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