Expression of CARD8 in human atherosclerosis and its regulation of inflammatory proteins in human endothelial cells
The Caspase activation and recruitment domain 8 (CARD8) protein is a component of innate immunity and overexpression of CARD8 mRNA was previously identified in atherosclerosis. However, very little is known about the regulation of CARD8 in endothelial cells and atherosclerosis. The aim of this study...
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| Veröffentlicht in: | Scientific reports 2020-11, Vol.10 (1), p.19108-19108, Article 19108 |
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| creator | Paramel, Geena V. Karadimou, Glykeria Eremo, Anna Göthlin Ljungberg, Liza U. Hedin, Ulf Olofsson, Peder S. Folkersen, Lasse Paulsson-Berne, Gabrielle Sirsjö, Allan Fransén, Karin |
| description | The Caspase activation and recruitment domain 8 (CARD8) protein is a component of innate immunity and overexpression of CARD8 mRNA was previously identified in atherosclerosis. However, very little is known about the regulation of CARD8 in endothelial cells and atherosclerosis. The aim of this study was to investigate CARD8 in the regulation of cytokine and chemokine expression in endothelial cells. Sections of human atherosclerotic lesions and non-atherosclerotic arteries were immunostained for CARD8 protein. Expression of CARD8 was correlated to mediators of inflammation in atherosclerotic lesions using Biobank of Karolinska Endarterectomies microarray data. The CARD8 mRNA was knocked-down in human umbilical vein endothelial cells (HUVECs) in vitro, followed by quantitative RT-PCR analysis and OLINK Proteomics. Endothelial and smooth muscle cells in arterial tissue expressed CARD8 and
CARD8
correlated with
vWF
,
CD163
and the expression of inflammatory genes, such as
CXCL1
,
CXCL6
and
PDGF-A
in plaque. Knock-down of CARD8 in HUVECs significantly altered proteins involved in inflammatory response, such as CXCL1, CXCL6, PDGF-A, MCP-1 and IL-6. The present study suggest that CARD8 regulate the expression of cytokines and chemokines in endothelial cells and atherosclerotic lesions, suggesting that CARD8 plays a significant role in endothelial activation. |
| doi_str_mv | 10.1038/s41598-020-73600-4 |
| format | Article |
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CARD8
correlated with
vWF
,
CD163
and the expression of inflammatory genes, such as
CXCL1
,
CXCL6
and
PDGF-A
in plaque. Knock-down of CARD8 in HUVECs significantly altered proteins involved in inflammatory response, such as CXCL1, CXCL6, PDGF-A, MCP-1 and IL-6. The present study suggest that CARD8 regulate the expression of cytokines and chemokines in endothelial cells and atherosclerotic lesions, suggesting that CARD8 plays a significant role in endothelial activation.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-73600-4</identifier><identifier>PMID: 33154409</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/250/127/1213 ; 631/250/2502 ; 631/250/256/2515 ; 631/250/262 ; 631/250/98 ; 631/80/304 ; 692/4019/592/75/593/2100 ; 692/53/2421 ; Arteries ; Arteriosclerosis ; Atherosclerosis ; Atherosclerosis - metabolism ; Atherosclerosis - surgery ; CARD Signaling Adaptor Proteins - metabolism ; CARD8 ; Carotid Arteries - metabolism ; Carotid Artery Diseases - metabolism ; Carotid Artery Diseases - surgery ; Caspase ; CD163 antigen ; Cell activation ; Chemokines ; Chemokines - metabolism ; chronic inflammation ; Cytokines - metabolism ; diagnostic markers ; Endarterectomy, Carotid ; Endothelial cells ; Endothelial Cells - metabolism ; Endothelium, Vascular - metabolism ; Humanities and Social Sciences ; Humans ; Inflammation ; Inflammation - metabolism ; Innate immunity ; Interleukin 6 ; interleukins ; Lesions ; mechanisms of disease ; Medicin ; Medicine ; Monocyte chemoattractant protein 1 ; mRNA ; multidisciplinary ; Muscle, Smooth, Vascular - metabolism ; Myocytes, Smooth Muscle - metabolism ; Neoplasm Proteins - metabolism ; Nitric oxide ; Plaque, Atherosclerotic - metabolism ; Plaque, Atherosclerotic - surgery ; Platelet-derived growth factor ; Polymerase chain reaction ; Proteomics ; Science ; Science (multidisciplinary) ; Smooth muscle ; Umbilical vein</subject><ispartof>Scientific reports, 2020-11, Vol.10 (1), p.19108-19108, Article 19108</ispartof><rights>The Author(s) 2020. corrected publication 2021</rights><rights>The Author(s) 2020. corrected publication 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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However, very little is known about the regulation of CARD8 in endothelial cells and atherosclerosis. The aim of this study was to investigate CARD8 in the regulation of cytokine and chemokine expression in endothelial cells. Sections of human atherosclerotic lesions and non-atherosclerotic arteries were immunostained for CARD8 protein. Expression of CARD8 was correlated to mediators of inflammation in atherosclerotic lesions using Biobank of Karolinska Endarterectomies microarray data. The CARD8 mRNA was knocked-down in human umbilical vein endothelial cells (HUVECs) in vitro, followed by quantitative RT-PCR analysis and OLINK Proteomics. Endothelial and smooth muscle cells in arterial tissue expressed CARD8 and
CARD8
correlated with
vWF
,
CD163
and the expression of inflammatory genes, such as
CXCL1
,
CXCL6
and
PDGF-A
in plaque. Knock-down of CARD8 in HUVECs significantly altered proteins involved in inflammatory response, such as CXCL1, CXCL6, PDGF-A, MCP-1 and IL-6. The present study suggest that CARD8 regulate the expression of cytokines and chemokines in endothelial cells and atherosclerotic lesions, suggesting that CARD8 plays a significant role in endothelial activation.</description><subject>631/250/127/1213</subject><subject>631/250/2502</subject><subject>631/250/256/2515</subject><subject>631/250/262</subject><subject>631/250/98</subject><subject>631/80/304</subject><subject>692/4019/592/75/593/2100</subject><subject>692/53/2421</subject><subject>Arteries</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Atherosclerosis - metabolism</subject><subject>Atherosclerosis - surgery</subject><subject>CARD Signaling Adaptor Proteins - metabolism</subject><subject>CARD8</subject><subject>Carotid Arteries - metabolism</subject><subject>Carotid Artery Diseases - metabolism</subject><subject>Carotid Artery Diseases - surgery</subject><subject>Caspase</subject><subject>CD163 antigen</subject><subject>Cell activation</subject><subject>Chemokines</subject><subject>Chemokines - metabolism</subject><subject>chronic inflammation</subject><subject>Cytokines - metabolism</subject><subject>diagnostic markers</subject><subject>Endarterectomy, Carotid</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation - metabolism</subject><subject>Innate immunity</subject><subject>Interleukin 6</subject><subject>interleukins</subject><subject>Lesions</subject><subject>mechanisms of disease</subject><subject>Medicin</subject><subject>Medicine</subject><subject>Monocyte chemoattractant protein 1</subject><subject>mRNA</subject><subject>multidisciplinary</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Nitric oxide</subject><subject>Plaque, Atherosclerotic - metabolism</subject><subject>Plaque, Atherosclerotic - surgery</subject><subject>Platelet-derived growth factor</subject><subject>Polymerase chain reaction</subject><subject>Proteomics</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Smooth muscle</subject><subject>Umbilical vein</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>D8T</sourceid><recordid>eNp9kttu1DAQhiMEolXpC3CBLHHDBaE-H26QVtsDlSpVQsCt5XWcXZfEXuyk0LfH6YYekFpLsUfxN38mM39VvUXwE4JEHmWKmJI1xLAWhENY0xfVPoaU1Zhg_PJBvFcd5nwFy2JYUaReV3uEIEYpVPtVPvmzTS5nHwOILVguvh5L4APYjL0JwAwbl2K23bT7DExogB8ySG49dmaYk3xoO9P3ZojpBmxTHJwP-V7EhSYWnc6bDljXdflN9ao1XXaH83lQfT89-bb8Ul9cnp0vFxe1ZUIMtbJWKgKdUAy1QmDHzGolFISCCtvIRlmOm9aWkNNV2yCCOOHGSsiUVa1oyUFV73Tzb7cdV3qbfG_SjY7G6_nVzxI5TTmXCBX-45P8sf-x0DGtyzNqKTCb8M87vLC9a6wLQzLdo6zHN8Fv9Dpea8Ep5ZIUgQ-zQIq_RpcH3fs8dcgEF8esMWWyjFrdou__Q6_imELpni6lUCnghD5HUVFGjpAQhcI7ypah5uTau5IR1JO39M5bunhL33pL05L07uHP3qX8c1IByNy8chXWLt1_-xnZv3ed2_c</recordid><startdate>20201105</startdate><enddate>20201105</enddate><creator>Paramel, Geena V.</creator><creator>Karadimou, Glykeria</creator><creator>Eremo, Anna Göthlin</creator><creator>Ljungberg, Liza U.</creator><creator>Hedin, Ulf</creator><creator>Olofsson, Peder S.</creator><creator>Folkersen, Lasse</creator><creator>Paulsson-Berne, Gabrielle</creator><creator>Sirsjö, Allan</creator><creator>Fransén, Karin</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>AABEP</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>D91</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0002-9826-0462</orcidid></search><sort><creationdate>20201105</creationdate><title>Expression of CARD8 in human atherosclerosis and its regulation of inflammatory proteins in human endothelial cells</title><author>Paramel, Geena V. ; Karadimou, Glykeria ; Eremo, Anna Göthlin ; Ljungberg, Liza U. ; Hedin, Ulf ; Olofsson, Peder S. ; Folkersen, Lasse ; Paulsson-Berne, Gabrielle ; Sirsjö, Allan ; Fransén, Karin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c577t-9cc8930e7951f772e5abb7900747cd8d9c62dfccd864bfd131636ac8059c9f7f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/250/127/1213</topic><topic>631/250/2502</topic><topic>631/250/256/2515</topic><topic>631/250/262</topic><topic>631/250/98</topic><topic>631/80/304</topic><topic>692/4019/592/75/593/2100</topic><topic>692/53/2421</topic><topic>Arteries</topic><topic>Arteriosclerosis</topic><topic>Atherosclerosis</topic><topic>Atherosclerosis - 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metabolism</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Nitric oxide</topic><topic>Plaque, Atherosclerotic - metabolism</topic><topic>Plaque, Atherosclerotic - surgery</topic><topic>Platelet-derived growth factor</topic><topic>Polymerase chain reaction</topic><topic>Proteomics</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Smooth muscle</topic><topic>Umbilical vein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Paramel, Geena V.</creatorcontrib><creatorcontrib>Karadimou, Glykeria</creatorcontrib><creatorcontrib>Eremo, Anna Göthlin</creatorcontrib><creatorcontrib>Ljungberg, Liza U.</creatorcontrib><creatorcontrib>Hedin, Ulf</creatorcontrib><creatorcontrib>Olofsson, Peder S.</creatorcontrib><creatorcontrib>Folkersen, Lasse</creatorcontrib><creatorcontrib>Paulsson-Berne, Gabrielle</creatorcontrib><creatorcontrib>Sirsjö, Allan</creatorcontrib><creatorcontrib>Fransén, Karin</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content 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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SWEPUB Örebro universitet full text</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Örebro universitet</collection><collection>SwePub Articles full text</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Paramel, Geena V.</au><au>Karadimou, Glykeria</au><au>Eremo, Anna Göthlin</au><au>Ljungberg, Liza U.</au><au>Hedin, Ulf</au><au>Olofsson, Peder S.</au><au>Folkersen, Lasse</au><au>Paulsson-Berne, Gabrielle</au><au>Sirsjö, Allan</au><au>Fransén, Karin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of CARD8 in human atherosclerosis and its regulation of inflammatory proteins in human endothelial cells</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-11-05</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>19108</spage><epage>19108</epage><pages>19108-19108</pages><artnum>19108</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The Caspase activation and recruitment domain 8 (CARD8) protein is a component of innate immunity and overexpression of CARD8 mRNA was previously identified in atherosclerosis. However, very little is known about the regulation of CARD8 in endothelial cells and atherosclerosis. The aim of this study was to investigate CARD8 in the regulation of cytokine and chemokine expression in endothelial cells. Sections of human atherosclerotic lesions and non-atherosclerotic arteries were immunostained for CARD8 protein. Expression of CARD8 was correlated to mediators of inflammation in atherosclerotic lesions using Biobank of Karolinska Endarterectomies microarray data. The CARD8 mRNA was knocked-down in human umbilical vein endothelial cells (HUVECs) in vitro, followed by quantitative RT-PCR analysis and OLINK Proteomics. Endothelial and smooth muscle cells in arterial tissue expressed CARD8 and
CARD8
correlated with
vWF
,
CD163
and the expression of inflammatory genes, such as
CXCL1
,
CXCL6
and
PDGF-A
in plaque. Knock-down of CARD8 in HUVECs significantly altered proteins involved in inflammatory response, such as CXCL1, CXCL6, PDGF-A, MCP-1 and IL-6. The present study suggest that CARD8 regulate the expression of cytokines and chemokines in endothelial cells and atherosclerotic lesions, suggesting that CARD8 plays a significant role in endothelial activation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33154409</pmid><doi>10.1038/s41598-020-73600-4</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-9826-0462</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Scientific reports, 2020-11, Vol.10 (1), p.19108-19108, Article 19108 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_466811 |
| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; SWEPUB Freely available online; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals |
| subjects | 631/250/127/1213 631/250/2502 631/250/256/2515 631/250/262 631/250/98 631/80/304 692/4019/592/75/593/2100 692/53/2421 Arteries Arteriosclerosis Atherosclerosis Atherosclerosis - metabolism Atherosclerosis - surgery CARD Signaling Adaptor Proteins - metabolism CARD8 Carotid Arteries - metabolism Carotid Artery Diseases - metabolism Carotid Artery Diseases - surgery Caspase CD163 antigen Cell activation Chemokines Chemokines - metabolism chronic inflammation Cytokines - metabolism diagnostic markers Endarterectomy, Carotid Endothelial cells Endothelial Cells - metabolism Endothelium, Vascular - metabolism Humanities and Social Sciences Humans Inflammation Inflammation - metabolism Innate immunity Interleukin 6 interleukins Lesions mechanisms of disease Medicin Medicine Monocyte chemoattractant protein 1 mRNA multidisciplinary Muscle, Smooth, Vascular - metabolism Myocytes, Smooth Muscle - metabolism Neoplasm Proteins - metabolism Nitric oxide Plaque, Atherosclerotic - metabolism Plaque, Atherosclerotic - surgery Platelet-derived growth factor Polymerase chain reaction Proteomics Science Science (multidisciplinary) Smooth muscle Umbilical vein |
| title | Expression of CARD8 in human atherosclerosis and its regulation of inflammatory proteins in human endothelial cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T02%3A23%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Expression%20of%20CARD8%20in%20human%20atherosclerosis%20and%20its%20regulation%20of%20inflammatory%20proteins%20in%20human%20endothelial%20cells&rft.jtitle=Scientific%20reports&rft.au=Paramel,%20Geena%20V.&rft.date=2020-11-05&rft.volume=10&rft.issue=1&rft.spage=19108&rft.epage=19108&rft.pages=19108-19108&rft.artnum=19108&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-020-73600-4&rft_dat=%3Cproquest_swepu%3E2458038983%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2471541177&rft_id=info:pmid/33154409&rfr_iscdi=true |