RNA-sequencing reveals that STRN, ZNF484 and WNK1 add to the value of mitochondrial MT-COI and COX10 as markers of unstable coronary artery disease
Markers in monocytes, precursors of macrophages, which are related to CAD, are largely unknown. Therefore, we aimed to identify genes in monocytes predictive of a new ischemic event in patients with CAD and/or discriminate between stable CAD and acute coronary syndrome. We included 66 patients with...
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| Veröffentlicht in: | PloS one 2019-12, Vol.14 (12), p.e0225621-e0225621 |
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| creator | Holvoet, Paul Klocke, Bernward Vanhaverbeke, Maarten Menten, Roxane Sinnaeve, Peter Raitoharju, Emma Lehtimäki, Terho Oksala, Niku Zinser, Christian Janssens, Stefan Sipido, Karin Lyytikainen, Leo-Pekka Cagnin, Stefano |
| description | Markers in monocytes, precursors of macrophages, which are related to CAD, are largely unknown. Therefore, we aimed to identify genes in monocytes predictive of a new ischemic event in patients with CAD and/or discriminate between stable CAD and acute coronary syndrome. We included 66 patients with stable CAD, of which 24 developed a new ischemic event, and 19 patients with ACS. Circulating CD14+ monocytes were isolated with magnetic beads. RNA sequencing analysis in monocytes of patients with (n = 13) versus without (n = 11) ischemic event at follow-up and in patients with ACS (n = 12) was validated with qPCR (n = 85). MT-COI, STRN and COX10 predicted new ischemic events in CAD patients (power for separation at 1% error rate of 0.97, 0.90 and 0.77 respectively). Low MT-COI and high STRN were also related to shorter time between blood sampling and event. COX10 and ZNF484 together with MT-COI, STRN and WNK1 separated ACS completely from stable CAD patients. RNA expressions in monocytes of MT-COI, COX10, STRN, WNK1 and ZNF484 were independent of cholesterol lowering and antiplatelet treatment. They were independent of troponin T, a marker of myocardial injury. But, COX10 and ZNF484 in human plaques correlated to plaque markers of M1 macrophage polarization, reflecting vascular injury. Expression of MT-COI, COX10, STRN and WNK1, but not that of ZNF484, PBMCs paired with that in monocytes. The prospective study of relation of MT-COI, COX10, STRN, WNK1 and ZNF484 with unstable CAD is warranted. |
| doi_str_mv | 10.1371/journal.pone.0225621 |
| format | Article |
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Therefore, we aimed to identify genes in monocytes predictive of a new ischemic event in patients with CAD and/or discriminate between stable CAD and acute coronary syndrome. We included 66 patients with stable CAD, of which 24 developed a new ischemic event, and 19 patients with ACS. Circulating CD14+ monocytes were isolated with magnetic beads. RNA sequencing analysis in monocytes of patients with (n = 13) versus without (n = 11) ischemic event at follow-up and in patients with ACS (n = 12) was validated with qPCR (n = 85). MT-COI, STRN and COX10 predicted new ischemic events in CAD patients (power for separation at 1% error rate of 0.97, 0.90 and 0.77 respectively). Low MT-COI and high STRN were also related to shorter time between blood sampling and event. COX10 and ZNF484 together with MT-COI, STRN and WNK1 separated ACS completely from stable CAD patients. RNA expressions in monocytes of MT-COI, COX10, STRN, WNK1 and ZNF484 were independent of cholesterol lowering and antiplatelet treatment. They were independent of troponin T, a marker of myocardial injury. But, COX10 and ZNF484 in human plaques correlated to plaque markers of M1 macrophage polarization, reflecting vascular injury. Expression of MT-COI, COX10, STRN and WNK1, but not that of ZNF484, PBMCs paired with that in monocytes. The prospective study of relation of MT-COI, COX10, STRN, WNK1 and ZNF484 with unstable CAD is warranted.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0225621</identifier><identifier>PMID: 31821324</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acute Coronary Syndrome - blood ; Acute Coronary Syndrome - diagnosis ; Acute Coronary Syndrome - pathology ; Aged ; Alkyl and Aryl Transferases - blood ; Alkyl and Aryl Transferases - metabolism ; Analysis ; Anticholesteremic agents ; Artificial intelligence ; Beads ; Bioinformatics ; Biology and Life Sciences ; Biomarkers ; Biomarkers - blood ; Biomarkers - metabolism ; Blood tests ; Calcium-binding protein ; Calmodulin-Binding Proteins - blood ; Calmodulin-Binding Proteins - metabolism ; Cardiology ; Cardiovascular disease ; CD14 antigen ; Cell adhesion & migration ; Cholesterol ; Cholesterol - blood ; Coronary Angiography ; Coronary artery ; Coronary artery disease ; Coronary Artery Disease - blood ; Coronary Artery Disease - diagnosis ; Coronary Artery Disease - pathology ; Coronary heart disease ; Coronary vessels ; Cytochrome ; Diagnosis, Differential ; Electron Transport Complex IV - blood ; Electron Transport Complex IV - metabolism ; Female ; Follow-Up Studies ; Gene expression ; Gene sequencing ; Genes ; Heart diseases ; Hospitals ; Humans ; Ischemia ; Laboratories ; Life sciences ; Machine learning ; Macrophages ; Male ; Medical research ; Medicine and Health Sciences ; Membrane Proteins - blood ; Membrane Proteins - metabolism ; Middle Aged ; Mitochondria ; Mitochondria - metabolism ; Monocytes ; Monocytes - cytology ; Monocytes - metabolism ; Nerve Tissue Proteins - blood ; Nerve Tissue Proteins - metabolism ; Plaque, Atherosclerotic - blood ; Plaque, Atherosclerotic - pathology ; Plaques ; Prospective Studies ; Research and analysis methods ; Ribonucleic acid ; RNA ; RNA sequencing ; RNA-Seq ; Troponin ; Troponin T ; Type 2 diabetes ; WNK Lysine-Deficient Protein Kinase 1 - blood ; WNK Lysine-Deficient Protein Kinase 1 - metabolism</subject><ispartof>PloS one, 2019-12, Vol.14 (12), p.e0225621-e0225621</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Holvoet et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Therefore, we aimed to identify genes in monocytes predictive of a new ischemic event in patients with CAD and/or discriminate between stable CAD and acute coronary syndrome. We included 66 patients with stable CAD, of which 24 developed a new ischemic event, and 19 patients with ACS. Circulating CD14+ monocytes were isolated with magnetic beads. RNA sequencing analysis in monocytes of patients with (n = 13) versus without (n = 11) ischemic event at follow-up and in patients with ACS (n = 12) was validated with qPCR (n = 85). MT-COI, STRN and COX10 predicted new ischemic events in CAD patients (power for separation at 1% error rate of 0.97, 0.90 and 0.77 respectively). Low MT-COI and high STRN were also related to shorter time between blood sampling and event. COX10 and ZNF484 together with MT-COI, STRN and WNK1 separated ACS completely from stable CAD patients. RNA expressions in monocytes of MT-COI, COX10, STRN, WNK1 and ZNF484 were independent of cholesterol lowering and antiplatelet treatment. They were independent of troponin T, a marker of myocardial injury. But, COX10 and ZNF484 in human plaques correlated to plaque markers of M1 macrophage polarization, reflecting vascular injury. Expression of MT-COI, COX10, STRN and WNK1, but not that of ZNF484, PBMCs paired with that in monocytes. The prospective study of relation of MT-COI, COX10, STRN, WNK1 and ZNF484 with unstable CAD is warranted.</description><subject>Acute Coronary Syndrome - blood</subject><subject>Acute Coronary Syndrome - diagnosis</subject><subject>Acute Coronary Syndrome - pathology</subject><subject>Aged</subject><subject>Alkyl and Aryl Transferases - blood</subject><subject>Alkyl and Aryl Transferases - metabolism</subject><subject>Analysis</subject><subject>Anticholesteremic agents</subject><subject>Artificial intelligence</subject><subject>Beads</subject><subject>Bioinformatics</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - metabolism</subject><subject>Blood tests</subject><subject>Calcium-binding protein</subject><subject>Calmodulin-Binding Proteins - blood</subject><subject>Calmodulin-Binding Proteins - metabolism</subject><subject>Cardiology</subject><subject>Cardiovascular disease</subject><subject>CD14 antigen</subject><subject>Cell adhesion & migration</subject><subject>Cholesterol</subject><subject>Cholesterol - blood</subject><subject>Coronary Angiography</subject><subject>Coronary artery</subject><subject>Coronary artery disease</subject><subject>Coronary Artery Disease - blood</subject><subject>Coronary Artery Disease - diagnosis</subject><subject>Coronary Artery Disease - pathology</subject><subject>Coronary heart disease</subject><subject>Coronary vessels</subject><subject>Cytochrome</subject><subject>Diagnosis, Differential</subject><subject>Electron Transport Complex IV - blood</subject><subject>Electron Transport Complex IV - metabolism</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gene expression</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Heart diseases</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Ischemia</subject><subject>Laboratories</subject><subject>Life sciences</subject><subject>Machine learning</subject><subject>Macrophages</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Membrane Proteins - blood</subject><subject>Membrane Proteins - metabolism</subject><subject>Middle Aged</subject><subject>Mitochondria</subject><subject>Mitochondria - metabolism</subject><subject>Monocytes</subject><subject>Monocytes - cytology</subject><subject>Monocytes - metabolism</subject><subject>Nerve Tissue Proteins - blood</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Plaque, Atherosclerotic - blood</subject><subject>Plaque, Atherosclerotic - pathology</subject><subject>Plaques</subject><subject>Prospective Studies</subject><subject>Research and analysis methods</subject><subject>Ribonucleic 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reveals that STRN, ZNF484 and WNK1 add to the value of mitochondrial MT-COI and COX10 as markers of unstable coronary artery disease</title><author>Holvoet, Paul ; Klocke, Bernward ; Vanhaverbeke, Maarten ; Menten, Roxane ; Sinnaeve, Peter ; Raitoharju, Emma ; Lehtimäki, Terho ; Oksala, Niku ; Zinser, Christian ; Janssens, Stefan ; Sipido, Karin ; Lyytikainen, Leo-Pekka ; Cagnin, Stefano</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-9ba97049bd84a2e37d2982112d60246521cbe53109ac3911c6b414149f6badb43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Acute Coronary Syndrome - blood</topic><topic>Acute Coronary Syndrome - diagnosis</topic><topic>Acute Coronary Syndrome - pathology</topic><topic>Aged</topic><topic>Alkyl and Aryl Transferases - blood</topic><topic>Alkyl and Aryl Transferases - metabolism</topic><topic>Analysis</topic><topic>Anticholesteremic agents</topic><topic>Artificial intelligence</topic><topic>Beads</topic><topic>Bioinformatics</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Biomarkers - metabolism</topic><topic>Blood tests</topic><topic>Calcium-binding protein</topic><topic>Calmodulin-Binding Proteins - blood</topic><topic>Calmodulin-Binding Proteins - metabolism</topic><topic>Cardiology</topic><topic>Cardiovascular disease</topic><topic>CD14 antigen</topic><topic>Cell adhesion & migration</topic><topic>Cholesterol</topic><topic>Cholesterol - blood</topic><topic>Coronary Angiography</topic><topic>Coronary artery</topic><topic>Coronary artery disease</topic><topic>Coronary Artery Disease - blood</topic><topic>Coronary Artery Disease - diagnosis</topic><topic>Coronary Artery Disease - pathology</topic><topic>Coronary heart disease</topic><topic>Coronary vessels</topic><topic>Cytochrome</topic><topic>Diagnosis, Differential</topic><topic>Electron Transport 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Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Holvoet, Paul</au><au>Klocke, Bernward</au><au>Vanhaverbeke, Maarten</au><au>Menten, Roxane</au><au>Sinnaeve, Peter</au><au>Raitoharju, Emma</au><au>Lehtimäki, Terho</au><au>Oksala, Niku</au><au>Zinser, Christian</au><au>Janssens, Stefan</au><au>Sipido, Karin</au><au>Lyytikainen, Leo-Pekka</au><au>Cagnin, Stefano</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RNA-sequencing reveals that STRN, ZNF484 and WNK1 add to the value of mitochondrial MT-COI and COX10 as markers of unstable coronary artery disease</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-12-10</date><risdate>2019</risdate><volume>14</volume><issue>12</issue><spage>e0225621</spage><epage>e0225621</epage><pages>e0225621-e0225621</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Markers in monocytes, precursors of macrophages, which are related to CAD, are largely unknown. Therefore, we aimed to identify genes in monocytes predictive of a new ischemic event in patients with CAD and/or discriminate between stable CAD and acute coronary syndrome. We included 66 patients with stable CAD, of which 24 developed a new ischemic event, and 19 patients with ACS. Circulating CD14+ monocytes were isolated with magnetic beads. RNA sequencing analysis in monocytes of patients with (n = 13) versus without (n = 11) ischemic event at follow-up and in patients with ACS (n = 12) was validated with qPCR (n = 85). MT-COI, STRN and COX10 predicted new ischemic events in CAD patients (power for separation at 1% error rate of 0.97, 0.90 and 0.77 respectively). Low MT-COI and high STRN were also related to shorter time between blood sampling and event. COX10 and ZNF484 together with MT-COI, STRN and WNK1 separated ACS completely from stable CAD patients. RNA expressions in monocytes of MT-COI, COX10, STRN, WNK1 and ZNF484 were independent of cholesterol lowering and antiplatelet treatment. They were independent of troponin T, a marker of myocardial injury. But, COX10 and ZNF484 in human plaques correlated to plaque markers of M1 macrophage polarization, reflecting vascular injury. Expression of MT-COI, COX10, STRN and WNK1, but not that of ZNF484, PBMCs paired with that in monocytes. The prospective study of relation of MT-COI, COX10, STRN, WNK1 and ZNF484 with unstable CAD is warranted.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31821324</pmid><doi>10.1371/journal.pone.0225621</doi><tpages>e0225621</tpages><orcidid>https://orcid.org/0000-0001-7271-4625</orcidid><orcidid>https://orcid.org/0000-0001-9201-0772</orcidid><orcidid>https://orcid.org/0000-0002-4385-7069</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2019-12, Vol.14 (12), p.e0225621-e0225621 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2323447069 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acute Coronary Syndrome - blood Acute Coronary Syndrome - diagnosis Acute Coronary Syndrome - pathology Aged Alkyl and Aryl Transferases - blood Alkyl and Aryl Transferases - metabolism Analysis Anticholesteremic agents Artificial intelligence Beads Bioinformatics Biology and Life Sciences Biomarkers Biomarkers - blood Biomarkers - metabolism Blood tests Calcium-binding protein Calmodulin-Binding Proteins - blood Calmodulin-Binding Proteins - metabolism Cardiology Cardiovascular disease CD14 antigen Cell adhesion & migration Cholesterol Cholesterol - blood Coronary Angiography Coronary artery Coronary artery disease Coronary Artery Disease - blood Coronary Artery Disease - diagnosis Coronary Artery Disease - pathology Coronary heart disease Coronary vessels Cytochrome Diagnosis, Differential Electron Transport Complex IV - blood Electron Transport Complex IV - metabolism Female Follow-Up Studies Gene expression Gene sequencing Genes Heart diseases Hospitals Humans Ischemia Laboratories Life sciences Machine learning Macrophages Male Medical research Medicine and Health Sciences Membrane Proteins - blood Membrane Proteins - metabolism Middle Aged Mitochondria Mitochondria - metabolism Monocytes Monocytes - cytology Monocytes - metabolism Nerve Tissue Proteins - blood Nerve Tissue Proteins - metabolism Plaque, Atherosclerotic - blood Plaque, Atherosclerotic - pathology Plaques Prospective Studies Research and analysis methods Ribonucleic acid RNA RNA sequencing RNA-Seq Troponin Troponin T Type 2 diabetes WNK Lysine-Deficient Protein Kinase 1 - blood WNK Lysine-Deficient Protein Kinase 1 - metabolism |
| title | RNA-sequencing reveals that STRN, ZNF484 and WNK1 add to the value of mitochondrial MT-COI and COX10 as markers of unstable coronary artery disease |
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