Impact of high platelet turnover on the platelet transcriptome: Results from platelet RNA-sequencing in patients with sepsis
Sepsis is associated with high platelet turnover and elevated levels of immature platelets. Changes in the platelet transcriptome and the specific impact of immature platelets on the platelet transcriptome remain unclear. Thus, this study sought to address whether and how elevated levels of immature...
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| Veröffentlicht in: | PloS one 2022-01, Vol.17 (1), p.e0260222-e0260222 |
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| creator | Nührenberg, Thomas G Stöckle, Jasmin Marini, Federico Zurek, Mark Grüning, Björn A Benes, Vladimir Hein, Lutz Neumann, Franz-Josef Stratz, Christian Cederqvist, Marco Hochholzer, Willibald |
| description | Sepsis is associated with high platelet turnover and elevated levels of immature platelets. Changes in the platelet transcriptome and the specific impact of immature platelets on the platelet transcriptome remain unclear. Thus, this study sought to address whether and how elevated levels of immature platelets affect the platelet transcriptome in patients with sepsis.
Blood samples were obtained from patients with sepsis requiring vasopressor therapy (n = 8) and from a control group of patients with stable coronary artery disease and otherwise similar demographic characteristics (n = 8). Immature platelet fraction (IPF) was determined on a Sysmex XE 2100 analyser and platelet function was tested by impedance aggregometry. RNA from leukocyte-depleted platelets was used for transcriptome analysis by Next Generation Sequencing integrating the use of unique molecular identifiers.
IPF (median [interquartile range]) was significantly elevated in sepsis patients (6.4 [5.3-8.7] % vs. 3.6 [2.6-4.6] %, p = 0.005). Platelet function testing revealed no differences in adenosine diphosphate- or thrombin receptor activating peptide-induced platelet aggregation between control and sepsis patients. Putative circular RNA transcripts were decreased in platelets from septic patients. Leukocyte contamination defined by CD45 abundance levels in RNA-sequencing was absent in both groups. Principal component analysis of transcripts showed only partial overlap of clustering with IPF levels. RNA sequencing showed up-regulation of 524 and down-regulation of 118 genes in platelets from sepsis patients compared to controls. Upregulated genes were mostly related to catabolic processes and protein translation. Comparison to published platelet transcriptomes showed a large overlap of changes observed in sepsis and COVID-19 but not with reticulated platelets from healthy donors.
Patients with sepsis appear to have a less degraded platelet transcriptome as indicated by increased levels of immature platelets and decreased levels of putative circular RNA transcripts. The present data suggests that increased protein translation is a characteristic mechanism of systemic inflammation. |
| doi_str_mv | 10.1371/journal.pone.0260222 |
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Blood samples were obtained from patients with sepsis requiring vasopressor therapy (n = 8) and from a control group of patients with stable coronary artery disease and otherwise similar demographic characteristics (n = 8). Immature platelet fraction (IPF) was determined on a Sysmex XE 2100 analyser and platelet function was tested by impedance aggregometry. RNA from leukocyte-depleted platelets was used for transcriptome analysis by Next Generation Sequencing integrating the use of unique molecular identifiers.
IPF (median [interquartile range]) was significantly elevated in sepsis patients (6.4 [5.3-8.7] % vs. 3.6 [2.6-4.6] %, p = 0.005). Platelet function testing revealed no differences in adenosine diphosphate- or thrombin receptor activating peptide-induced platelet aggregation between control and sepsis patients. Putative circular RNA transcripts were decreased in platelets from septic patients. Leukocyte contamination defined by CD45 abundance levels in RNA-sequencing was absent in both groups. Principal component analysis of transcripts showed only partial overlap of clustering with IPF levels. RNA sequencing showed up-regulation of 524 and down-regulation of 118 genes in platelets from sepsis patients compared to controls. Upregulated genes were mostly related to catabolic processes and protein translation. Comparison to published platelet transcriptomes showed a large overlap of changes observed in sepsis and COVID-19 but not with reticulated platelets from healthy donors.
Patients with sepsis appear to have a less degraded platelet transcriptome as indicated by increased levels of immature platelets and decreased levels of putative circular RNA transcripts. The present data suggests that increased protein translation is a characteristic mechanism of systemic inflammation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0260222</identifier><identifier>PMID: 35085240</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenosine ; Adenosine diphosphate ; Aged ; Base Sequence - genetics ; Biology and Life Sciences ; Blood platelets ; Blood Platelets - metabolism ; Blood Platelets - pathology ; Cardiovascular disease ; CD45 antigen ; Cell Fractionation - methods ; Circular RNA ; Clustering ; Complications and side effects ; Contamination ; Coronary artery ; Coronary artery disease ; Coronary vessels ; COVID-19 ; Data analysis ; Down-regulation ; Gene Expression - genetics ; Gene Expression Profiling - methods ; Gene regulation ; Gene sequencing ; Genes ; Genetic aspects ; Health aspects ; Heart diseases ; Humans ; Leukocytes ; Male ; Medical imaging ; Medicine and Health Sciences ; Next-generation sequencing ; Patients ; Physical Sciences ; Platelet Activation - genetics ; Platelet aggregation ; Platelet Aggregation - drug effects ; Platelet Aggregation Inhibitors - pharmacology ; Platelet Count ; Platelet Function Tests ; Platelets ; Principal components analysis ; Proteins ; Research and analysis methods ; Ribonucleic acid ; RNA ; RNA sequencing ; RNA, Circular - analysis ; RNA, Circular - genetics ; Sepsis ; Sepsis - blood ; Sepsis - genetics ; Sequence Analysis, RNA - methods ; Statistical analysis ; Thrombin ; Transcriptome - genetics ; Transcriptomes ; Translation ; Vein & artery diseases</subject><ispartof>PloS one, 2022-01, Vol.17 (1), p.e0260222-e0260222</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Nührenberg 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. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 Nührenberg et al 2022 Nührenberg et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-14c881940d52b73238999211568db8636a29db756042c9395a1caf485657ba043</citedby><cites>FETCH-LOGICAL-c692t-14c881940d52b73238999211568db8636a29db756042c9395a1caf485657ba043</cites><orcidid>0000-0002-0921-8351 ; 0000-0003-3252-7758 ; 0000-0001-7675-7120</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8794123/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8794123/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35085240$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nührenberg, Thomas G</creatorcontrib><creatorcontrib>Stöckle, Jasmin</creatorcontrib><creatorcontrib>Marini, Federico</creatorcontrib><creatorcontrib>Zurek, Mark</creatorcontrib><creatorcontrib>Grüning, Björn A</creatorcontrib><creatorcontrib>Benes, Vladimir</creatorcontrib><creatorcontrib>Hein, Lutz</creatorcontrib><creatorcontrib>Neumann, Franz-Josef</creatorcontrib><creatorcontrib>Stratz, Christian</creatorcontrib><creatorcontrib>Cederqvist, Marco</creatorcontrib><creatorcontrib>Hochholzer, Willibald</creatorcontrib><title>Impact of high platelet turnover on the platelet transcriptome: Results from platelet RNA-sequencing in patients with sepsis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Sepsis is associated with high platelet turnover and elevated levels of immature platelets. Changes in the platelet transcriptome and the specific impact of immature platelets on the platelet transcriptome remain unclear. Thus, this study sought to address whether and how elevated levels of immature platelets affect the platelet transcriptome in patients with sepsis.
Blood samples were obtained from patients with sepsis requiring vasopressor therapy (n = 8) and from a control group of patients with stable coronary artery disease and otherwise similar demographic characteristics (n = 8). Immature platelet fraction (IPF) was determined on a Sysmex XE 2100 analyser and platelet function was tested by impedance aggregometry. RNA from leukocyte-depleted platelets was used for transcriptome analysis by Next Generation Sequencing integrating the use of unique molecular identifiers.
IPF (median [interquartile range]) was significantly elevated in sepsis patients (6.4 [5.3-8.7] % vs. 3.6 [2.6-4.6] %, p = 0.005). Platelet function testing revealed no differences in adenosine diphosphate- or thrombin receptor activating peptide-induced platelet aggregation between control and sepsis patients. Putative circular RNA transcripts were decreased in platelets from septic patients. Leukocyte contamination defined by CD45 abundance levels in RNA-sequencing was absent in both groups. Principal component analysis of transcripts showed only partial overlap of clustering with IPF levels. RNA sequencing showed up-regulation of 524 and down-regulation of 118 genes in platelets from sepsis patients compared to controls. Upregulated genes were mostly related to catabolic processes and protein translation. Comparison to published platelet transcriptomes showed a large overlap of changes observed in sepsis and COVID-19 but not with reticulated platelets from healthy donors.
Patients with sepsis appear to have a less degraded platelet transcriptome as indicated by increased levels of immature platelets and decreased levels of putative circular RNA transcripts. The present data suggests that increased protein translation is a characteristic mechanism of systemic inflammation.</description><subject>Adenosine</subject><subject>Adenosine diphosphate</subject><subject>Aged</subject><subject>Base Sequence - genetics</subject><subject>Biology and Life Sciences</subject><subject>Blood platelets</subject><subject>Blood Platelets - metabolism</subject><subject>Blood Platelets - pathology</subject><subject>Cardiovascular disease</subject><subject>CD45 antigen</subject><subject>Cell Fractionation - methods</subject><subject>Circular RNA</subject><subject>Clustering</subject><subject>Complications and side effects</subject><subject>Contamination</subject><subject>Coronary artery</subject><subject>Coronary artery disease</subject><subject>Coronary vessels</subject><subject>COVID-19</subject><subject>Data analysis</subject><subject>Down-regulation</subject><subject>Gene Expression - genetics</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene regulation</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Heart diseases</subject><subject>Humans</subject><subject>Leukocytes</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Medicine and Health Sciences</subject><subject>Next-generation sequencing</subject><subject>Patients</subject><subject>Physical Sciences</subject><subject>Platelet Activation - genetics</subject><subject>Platelet aggregation</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelet Aggregation Inhibitors - pharmacology</subject><subject>Platelet Count</subject><subject>Platelet Function Tests</subject><subject>Platelets</subject><subject>Principal components analysis</subject><subject>Proteins</subject><subject>Research and analysis methods</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA sequencing</subject><subject>RNA, Circular - analysis</subject><subject>RNA, Circular - genetics</subject><subject>Sepsis</subject><subject>Sepsis - blood</subject><subject>Sepsis - genetics</subject><subject>Sequence Analysis, RNA - methods</subject><subject>Statistical analysis</subject><subject>Thrombin</subject><subject>Transcriptome - genetics</subject><subject>Transcriptomes</subject><subject>Translation</subject><subject>Vein & artery diseases</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1uL1DAUgIso7jr6D0QLgujDjLk1k_ggDIuXgcWF8fIa0jRts6RNTdJVwR9vxumuU9kH6UNK8p3v5Jz2ZNljCFYQr-GrSzf6XtrV4Hq9AogChNCd7BRyjJYUAXz36P0kexDCJQAFZpTez05wAViBCDjNfm27QaqYuzpvTdPmg5VRWx3zmOzuSvvc9Xls9dGBl31Q3gzRdfp1vtNhtDHktXfdX2j3cbMM-tuoe2X6Jjd9PshodJ_A7ya2edBDMOFhdq-WNuhH07rIvrx7-_nsw_L84v32bHO-VJSjuIREMQY5AVWByjVGmHHOEYQFZVXJKKYS8apcFxQQpDjmhYRK1oQVtFiXEhC8yJ4evIN1QUyNCwJRhDHByZWI7YGonLwUgzed9D-Fk0b82XC-EdJHo6wWBCLFYMl1CWtCOGSgXNe0LBRXFS4qmlxvpmxj2elKpaq9tDPp_KQ3rWjclWBrnuQ4CV5MAu9SC0MUnQlKWyt77cbDvRkjGPGEPvsHvb26iWpkKsD0tUt51V4qNpQDytA-7yJb3UKlp9KdUekvq03anwW8nAUkJuofsZFjCGL7aff_7MXXOfv8iG21tLENzo7RuD7MQXIAlXcheF3fNBkCsR-S626I_ZCIaUhS2JPjD3QTdD0V-DfyAQw3</recordid><startdate>20220127</startdate><enddate>20220127</enddate><creator>Nührenberg, Thomas G</creator><creator>Stöckle, Jasmin</creator><creator>Marini, Federico</creator><creator>Zurek, Mark</creator><creator>Grüning, Björn A</creator><creator>Benes, Vladimir</creator><creator>Hein, Lutz</creator><creator>Neumann, Franz-Josef</creator><creator>Stratz, Christian</creator><creator>Cederqvist, Marco</creator><creator>Hochholzer, Willibald</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>COVID</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-0921-8351</orcidid><orcidid>https://orcid.org/0000-0003-3252-7758</orcidid><orcidid>https://orcid.org/0000-0001-7675-7120</orcidid></search><sort><creationdate>20220127</creationdate><title>Impact of high platelet turnover on the platelet transcriptome: Results from platelet RNA-sequencing in patients with sepsis</title><author>Nührenberg, Thomas G ; Stöckle, Jasmin ; Marini, Federico ; Zurek, Mark ; Grüning, Björn A ; Benes, Vladimir ; Hein, Lutz ; Neumann, Franz-Josef ; Stratz, Christian ; Cederqvist, Marco ; Hochholzer, Willibald</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-14c881940d52b73238999211568db8636a29db756042c9395a1caf485657ba043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adenosine</topic><topic>Adenosine diphosphate</topic><topic>Aged</topic><topic>Base Sequence - genetics</topic><topic>Biology and Life Sciences</topic><topic>Blood platelets</topic><topic>Blood Platelets - metabolism</topic><topic>Blood Platelets - pathology</topic><topic>Cardiovascular disease</topic><topic>CD45 antigen</topic><topic>Cell Fractionation - methods</topic><topic>Circular RNA</topic><topic>Clustering</topic><topic>Complications and side effects</topic><topic>Contamination</topic><topic>Coronary artery</topic><topic>Coronary artery disease</topic><topic>Coronary vessels</topic><topic>COVID-19</topic><topic>Data analysis</topic><topic>Down-regulation</topic><topic>Gene Expression - genetics</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene regulation</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Heart diseases</topic><topic>Humans</topic><topic>Leukocytes</topic><topic>Male</topic><topic>Medical imaging</topic><topic>Medicine and Health Sciences</topic><topic>Next-generation sequencing</topic><topic>Patients</topic><topic>Physical Sciences</topic><topic>Platelet Activation - genetics</topic><topic>Platelet aggregation</topic><topic>Platelet Aggregation - drug effects</topic><topic>Platelet Aggregation Inhibitors - pharmacology</topic><topic>Platelet Count</topic><topic>Platelet Function Tests</topic><topic>Platelets</topic><topic>Principal components analysis</topic><topic>Proteins</topic><topic>Research and analysis methods</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA sequencing</topic><topic>RNA, Circular - analysis</topic><topic>RNA, Circular - genetics</topic><topic>Sepsis</topic><topic>Sepsis - blood</topic><topic>Sepsis - genetics</topic><topic>Sequence Analysis, RNA - methods</topic><topic>Statistical analysis</topic><topic>Thrombin</topic><topic>Transcriptome - genetics</topic><topic>Transcriptomes</topic><topic>Translation</topic><topic>Vein & artery diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nührenberg, Thomas G</creatorcontrib><creatorcontrib>Stöckle, Jasmin</creatorcontrib><creatorcontrib>Marini, Federico</creatorcontrib><creatorcontrib>Zurek, Mark</creatorcontrib><creatorcontrib>Grüning, Björn A</creatorcontrib><creatorcontrib>Benes, Vladimir</creatorcontrib><creatorcontrib>Hein, Lutz</creatorcontrib><creatorcontrib>Neumann, Franz-Josef</creatorcontrib><creatorcontrib>Stratz, Christian</creatorcontrib><creatorcontrib>Cederqvist, Marco</creatorcontrib><creatorcontrib>Hochholzer, Willibald</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints in Context (Gale)</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</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>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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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>Nührenberg, Thomas G</au><au>Stöckle, Jasmin</au><au>Marini, Federico</au><au>Zurek, Mark</au><au>Grüning, Björn A</au><au>Benes, Vladimir</au><au>Hein, Lutz</au><au>Neumann, Franz-Josef</au><au>Stratz, Christian</au><au>Cederqvist, Marco</au><au>Hochholzer, Willibald</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of high platelet turnover on the platelet transcriptome: Results from platelet RNA-sequencing in patients with sepsis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2022-01-27</date><risdate>2022</risdate><volume>17</volume><issue>1</issue><spage>e0260222</spage><epage>e0260222</epage><pages>e0260222-e0260222</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Sepsis is associated with high platelet turnover and elevated levels of immature platelets. Changes in the platelet transcriptome and the specific impact of immature platelets on the platelet transcriptome remain unclear. Thus, this study sought to address whether and how elevated levels of immature platelets affect the platelet transcriptome in patients with sepsis.
Blood samples were obtained from patients with sepsis requiring vasopressor therapy (n = 8) and from a control group of patients with stable coronary artery disease and otherwise similar demographic characteristics (n = 8). Immature platelet fraction (IPF) was determined on a Sysmex XE 2100 analyser and platelet function was tested by impedance aggregometry. RNA from leukocyte-depleted platelets was used for transcriptome analysis by Next Generation Sequencing integrating the use of unique molecular identifiers.
IPF (median [interquartile range]) was significantly elevated in sepsis patients (6.4 [5.3-8.7] % vs. 3.6 [2.6-4.6] %, p = 0.005). Platelet function testing revealed no differences in adenosine diphosphate- or thrombin receptor activating peptide-induced platelet aggregation between control and sepsis patients. Putative circular RNA transcripts were decreased in platelets from septic patients. Leukocyte contamination defined by CD45 abundance levels in RNA-sequencing was absent in both groups. Principal component analysis of transcripts showed only partial overlap of clustering with IPF levels. RNA sequencing showed up-regulation of 524 and down-regulation of 118 genes in platelets from sepsis patients compared to controls. Upregulated genes were mostly related to catabolic processes and protein translation. Comparison to published platelet transcriptomes showed a large overlap of changes observed in sepsis and COVID-19 but not with reticulated platelets from healthy donors.
Patients with sepsis appear to have a less degraded platelet transcriptome as indicated by increased levels of immature platelets and decreased levels of putative circular RNA transcripts. The present data suggests that increased protein translation is a characteristic mechanism of systemic inflammation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>35085240</pmid><doi>10.1371/journal.pone.0260222</doi><tpages>e0260222</tpages><orcidid>https://orcid.org/0000-0002-0921-8351</orcidid><orcidid>https://orcid.org/0000-0003-3252-7758</orcidid><orcidid>https://orcid.org/0000-0001-7675-7120</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2022-01, Vol.17 (1), p.e0260222-e0260222 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2623343992 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenosine Adenosine diphosphate Aged Base Sequence - genetics Biology and Life Sciences Blood platelets Blood Platelets - metabolism Blood Platelets - pathology Cardiovascular disease CD45 antigen Cell Fractionation - methods Circular RNA Clustering Complications and side effects Contamination Coronary artery Coronary artery disease Coronary vessels COVID-19 Data analysis Down-regulation Gene Expression - genetics Gene Expression Profiling - methods Gene regulation Gene sequencing Genes Genetic aspects Health aspects Heart diseases Humans Leukocytes Male Medical imaging Medicine and Health Sciences Next-generation sequencing Patients Physical Sciences Platelet Activation - genetics Platelet aggregation Platelet Aggregation - drug effects Platelet Aggregation Inhibitors - pharmacology Platelet Count Platelet Function Tests Platelets Principal components analysis Proteins Research and analysis methods Ribonucleic acid RNA RNA sequencing RNA, Circular - analysis RNA, Circular - genetics Sepsis Sepsis - blood Sepsis - genetics Sequence Analysis, RNA - methods Statistical analysis Thrombin Transcriptome - genetics Transcriptomes Translation Vein & artery diseases |
| title | Impact of high platelet turnover on the platelet transcriptome: Results from platelet RNA-sequencing in patients with sepsis |
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