Increased Atherosclerotic Lesions in LDL Receptor Deficient Mice With Hematopoietic Nuclear Receptor Rev‐erbα Knock‐ Down
Background Nuclear receptor Rev‐erbα plays important roles in circadian clock timing, lipid metabolism, adipogenesis, and vascular inflammation. However, the role of Rev‐erbα in atherosclerotic lesion development has not been assessed in vivo. Methods and Results The nuclear receptor Rev‐erbα was kn...
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| Veröffentlicht in: | Journal of the American Heart Association 2013-08, Vol.2 (4), p.e000235-n/a |
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| creator | Ma, Hongling Zhong, Wenbin Jiang, Yingliang Fontaine, Coralie Li, Shiqian Fu, Jiangnan Olkkonen, Vesa M. Staels, Bart Yan, Daoguang |
| description | Background
Nuclear receptor Rev‐erbα plays important roles in circadian clock timing, lipid metabolism, adipogenesis, and vascular inflammation. However, the role of Rev‐erbα in atherosclerotic lesion development has not been assessed in vivo.
Methods and Results
The nuclear receptor Rev‐erbα was knocked down in mouse haematopoietic cells by means of shRNA‐lentiviral transduction, followed by bone marrow transplantation into LDL receptor knockout mice. The Rev‐erbα protein in peripheral macrophage was reduced by 70% as compared to control mice injected with nontargeting shRNA lentivirus‐transduced bone marrow. A significant increase in atherosclerotic lesions was observed around the aorta valves as well as upon en face aorta analysis of Rev‐erbα knock‐down bone marrow recipients (P |
| doi_str_mv | 10.1161/JAHA.113.000235 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3828791</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1426999540</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4387-9592fdcda695a0e8296693c17572c1baa2bafff68250c9474d1b4c35cea229b73</originalsourceid><addsrcrecordid>eNqFkc1OGzEUha2qVUGUdXfIy24C_hnb402liLQNMFAJterS8njuELeTcbAnIDYVj8Cr8CI8BE-Co_DXVTf2ufJ3j699EPpIyS6lku4djqfjrPguIYRx8QZtMlKokdYleftKb6DtlH5nhkimuNDv0QbjWnIlxCb6e9C7CDZBg8fDDGJIrsvr4B2uIPnQJ-x7XE0qfAoOFkOIeAKtdx76AR97B_iXH2Z4CnM7hEXwsOo8WWYTG19aTuHi_voGYn13i4_64P7kCk_CZf8BvWttl2D7cd9CP79--bE_HVXfvx3sj6uRK3iZnyE0axvXWKmFJVAyLaXmjiqhmKO1tay2bdvKkgnidKGKhtaF48KBZUzXim-hz2vfxbKeQ-Py9NF2ZhH93MYrE6w3_570fmbOwoXhJSuVptng06NBDOdLSIOZ--Sg62wPYZkMLZjUWouCZHRvjbr8mylC-3wNJWYVnFkFlxU36-Byx87r6Z75p5gyUKyBS9_B1f_8VjVnUvEHGFGnjQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1426999540</pqid></control><display><type>article</type><title>Increased Atherosclerotic Lesions in LDL Receptor Deficient Mice With Hematopoietic Nuclear Receptor Rev‐erbα Knock‐ Down</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Wiley Online Library Open Access</source><source>PubMed Central</source><creator>Ma, Hongling ; Zhong, Wenbin ; Jiang, Yingliang ; Fontaine, Coralie ; Li, Shiqian ; Fu, Jiangnan ; Olkkonen, Vesa M. ; Staels, Bart ; Yan, Daoguang</creator><creatorcontrib>Ma, Hongling ; Zhong, Wenbin ; Jiang, Yingliang ; Fontaine, Coralie ; Li, Shiqian ; Fu, Jiangnan ; Olkkonen, Vesa M. ; Staels, Bart ; Yan, Daoguang</creatorcontrib><description>Background
Nuclear receptor Rev‐erbα plays important roles in circadian clock timing, lipid metabolism, adipogenesis, and vascular inflammation. However, the role of Rev‐erbα in atherosclerotic lesion development has not been assessed in vivo.
Methods and Results
The nuclear receptor Rev‐erbα was knocked down in mouse haematopoietic cells by means of shRNA‐lentiviral transduction, followed by bone marrow transplantation into LDL receptor knockout mice. The Rev‐erbα protein in peripheral macrophage was reduced by 70% as compared to control mice injected with nontargeting shRNA lentivirus‐transduced bone marrow. A significant increase in atherosclerotic lesions was observed around the aorta valves as well as upon en face aorta analysis of Rev‐erbα knock‐down bone marrow recipients (P<0.01) as compared to the control mice, while plasma cholesterol, phospholipid, and triacylglycerol levels were not affected. Overexpression of Rev‐erbα in bone marrow mononuclear cells decreased inflammatory M1 while increasing M2 macrophage markers, while Rev‐erbα knock down increased the macrophage inflammatory phenotype in vitro and in vivo. Furthermore, treatment of differentiating macrophages with the Rev‐erbα ligand heme promoted expression of antiinflammatory M2 markers.
Conclusions
These observations identify hematopoietic cell Rev‐erbα as a new modulator of atherogenesis in mice.</description><identifier>ISSN: 2047-9980</identifier><identifier>EISSN: 2047-9980</identifier><identifier>DOI: 10.1161/JAHA.113.000235</identifier><identifier>PMID: 23963755</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Animals ; Aorta - immunology ; Aorta - metabolism ; Aorta - pathology ; Aortic Diseases - genetics ; Aortic Diseases - immunology ; Aortic Diseases - metabolism ; Aortic Diseases - pathology ; atherosclerosis ; Atherosclerosis - genetics ; Atherosclerosis - immunology ; Atherosclerosis - metabolism ; Atherosclerosis - pathology ; Bone Marrow Transplantation ; Cells, Cultured ; Disease Models, Animal ; Gene Knockdown Techniques ; Genetic Vectors ; Genotype ; Inflammation Mediators - metabolism ; Lentivirus - genetics ; Lipids - blood ; Macrophage Activation ; macrophages ; Macrophages - immunology ; Macrophages - metabolism ; Macrophages - pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nuclear Receptor Subfamily 1, Group D, Member 1 - deficiency ; Nuclear Receptor Subfamily 1, Group D, Member 1 - genetics ; Original Research ; Phenotype ; Receptors, LDL - deficiency ; Receptors, LDL - genetics ; Rev‐erbα ; RNA Interference ; Transduction, Genetic</subject><ispartof>Journal of the American Heart Association, 2013-08, Vol.2 (4), p.e000235-n/a</ispartof><rights>2013 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley‐Blackwell.</rights><rights>2013 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley-Blackwell. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4387-9592fdcda695a0e8296693c17572c1baa2bafff68250c9474d1b4c35cea229b73</citedby><cites>FETCH-LOGICAL-c4387-9592fdcda695a0e8296693c17572c1baa2bafff68250c9474d1b4c35cea229b73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828791/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828791/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,11562,27924,27925,46052,46476,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23963755$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Hongling</creatorcontrib><creatorcontrib>Zhong, Wenbin</creatorcontrib><creatorcontrib>Jiang, Yingliang</creatorcontrib><creatorcontrib>Fontaine, Coralie</creatorcontrib><creatorcontrib>Li, Shiqian</creatorcontrib><creatorcontrib>Fu, Jiangnan</creatorcontrib><creatorcontrib>Olkkonen, Vesa M.</creatorcontrib><creatorcontrib>Staels, Bart</creatorcontrib><creatorcontrib>Yan, Daoguang</creatorcontrib><title>Increased Atherosclerotic Lesions in LDL Receptor Deficient Mice With Hematopoietic Nuclear Receptor Rev‐erbα Knock‐ Down</title><title>Journal of the American Heart Association</title><addtitle>J Am Heart Assoc</addtitle><description>Background
Nuclear receptor Rev‐erbα plays important roles in circadian clock timing, lipid metabolism, adipogenesis, and vascular inflammation. However, the role of Rev‐erbα in atherosclerotic lesion development has not been assessed in vivo.
Methods and Results
The nuclear receptor Rev‐erbα was knocked down in mouse haematopoietic cells by means of shRNA‐lentiviral transduction, followed by bone marrow transplantation into LDL receptor knockout mice. The Rev‐erbα protein in peripheral macrophage was reduced by 70% as compared to control mice injected with nontargeting shRNA lentivirus‐transduced bone marrow. A significant increase in atherosclerotic lesions was observed around the aorta valves as well as upon en face aorta analysis of Rev‐erbα knock‐down bone marrow recipients (P<0.01) as compared to the control mice, while plasma cholesterol, phospholipid, and triacylglycerol levels were not affected. Overexpression of Rev‐erbα in bone marrow mononuclear cells decreased inflammatory M1 while increasing M2 macrophage markers, while Rev‐erbα knock down increased the macrophage inflammatory phenotype in vitro and in vivo. Furthermore, treatment of differentiating macrophages with the Rev‐erbα ligand heme promoted expression of antiinflammatory M2 markers.
Conclusions
These observations identify hematopoietic cell Rev‐erbα as a new modulator of atherogenesis in mice.</description><subject>Animals</subject><subject>Aorta - immunology</subject><subject>Aorta - metabolism</subject><subject>Aorta - pathology</subject><subject>Aortic Diseases - genetics</subject><subject>Aortic Diseases - immunology</subject><subject>Aortic Diseases - metabolism</subject><subject>Aortic Diseases - pathology</subject><subject>atherosclerosis</subject><subject>Atherosclerosis - genetics</subject><subject>Atherosclerosis - immunology</subject><subject>Atherosclerosis - metabolism</subject><subject>Atherosclerosis - pathology</subject><subject>Bone Marrow Transplantation</subject><subject>Cells, Cultured</subject><subject>Disease Models, Animal</subject><subject>Gene Knockdown Techniques</subject><subject>Genetic Vectors</subject><subject>Genotype</subject><subject>Inflammation Mediators - metabolism</subject><subject>Lentivirus - genetics</subject><subject>Lipids - blood</subject><subject>Macrophage Activation</subject><subject>macrophages</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Macrophages - pathology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Nuclear Receptor Subfamily 1, Group D, Member 1 - deficiency</subject><subject>Nuclear Receptor Subfamily 1, Group D, Member 1 - genetics</subject><subject>Original Research</subject><subject>Phenotype</subject><subject>Receptors, LDL - deficiency</subject><subject>Receptors, LDL - genetics</subject><subject>Rev‐erbα</subject><subject>RNA Interference</subject><subject>Transduction, Genetic</subject><issn>2047-9980</issn><issn>2047-9980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNqFkc1OGzEUha2qVUGUdXfIy24C_hnb402liLQNMFAJterS8njuELeTcbAnIDYVj8Cr8CI8BE-Co_DXVTf2ufJ3j699EPpIyS6lku4djqfjrPguIYRx8QZtMlKokdYleftKb6DtlH5nhkimuNDv0QbjWnIlxCb6e9C7CDZBg8fDDGJIrsvr4B2uIPnQJ-x7XE0qfAoOFkOIeAKtdx76AR97B_iXH2Z4CnM7hEXwsOo8WWYTG19aTuHi_voGYn13i4_64P7kCk_CZf8BvWttl2D7cd9CP79--bE_HVXfvx3sj6uRK3iZnyE0axvXWKmFJVAyLaXmjiqhmKO1tay2bdvKkgnidKGKhtaF48KBZUzXim-hz2vfxbKeQ-Py9NF2ZhH93MYrE6w3_570fmbOwoXhJSuVptng06NBDOdLSIOZ--Sg62wPYZkMLZjUWouCZHRvjbr8mylC-3wNJWYVnFkFlxU36-Byx87r6Z75p5gyUKyBS9_B1f_8VjVnUvEHGFGnjQ</recordid><startdate>20130820</startdate><enddate>20130820</enddate><creator>Ma, Hongling</creator><creator>Zhong, Wenbin</creator><creator>Jiang, Yingliang</creator><creator>Fontaine, Coralie</creator><creator>Li, Shiqian</creator><creator>Fu, Jiangnan</creator><creator>Olkkonen, Vesa M.</creator><creator>Staels, Bart</creator><creator>Yan, Daoguang</creator><general>Blackwell Publishing Ltd</general><scope>24P</scope><scope>WIN</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130820</creationdate><title>Increased Atherosclerotic Lesions in LDL Receptor Deficient Mice With Hematopoietic Nuclear Receptor Rev‐erbα Knock‐ Down</title><author>Ma, Hongling ; Zhong, Wenbin ; Jiang, Yingliang ; Fontaine, Coralie ; Li, Shiqian ; Fu, Jiangnan ; Olkkonen, Vesa M. ; Staels, Bart ; Yan, Daoguang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4387-9592fdcda695a0e8296693c17572c1baa2bafff68250c9474d1b4c35cea229b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Aorta - immunology</topic><topic>Aorta - metabolism</topic><topic>Aorta - pathology</topic><topic>Aortic Diseases - genetics</topic><topic>Aortic Diseases - immunology</topic><topic>Aortic Diseases - metabolism</topic><topic>Aortic Diseases - pathology</topic><topic>atherosclerosis</topic><topic>Atherosclerosis - genetics</topic><topic>Atherosclerosis - immunology</topic><topic>Atherosclerosis - metabolism</topic><topic>Atherosclerosis - pathology</topic><topic>Bone Marrow Transplantation</topic><topic>Cells, Cultured</topic><topic>Disease Models, Animal</topic><topic>Gene Knockdown Techniques</topic><topic>Genetic Vectors</topic><topic>Genotype</topic><topic>Inflammation Mediators - metabolism</topic><topic>Lentivirus - genetics</topic><topic>Lipids - blood</topic><topic>Macrophage Activation</topic><topic>macrophages</topic><topic>Macrophages - immunology</topic><topic>Macrophages - metabolism</topic><topic>Macrophages - pathology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Nuclear Receptor Subfamily 1, Group D, Member 1 - deficiency</topic><topic>Nuclear Receptor Subfamily 1, Group D, Member 1 - genetics</topic><topic>Original Research</topic><topic>Phenotype</topic><topic>Receptors, LDL - deficiency</topic><topic>Receptors, LDL - genetics</topic><topic>Rev‐erbα</topic><topic>RNA Interference</topic><topic>Transduction, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Hongling</creatorcontrib><creatorcontrib>Zhong, Wenbin</creatorcontrib><creatorcontrib>Jiang, Yingliang</creatorcontrib><creatorcontrib>Fontaine, Coralie</creatorcontrib><creatorcontrib>Li, Shiqian</creatorcontrib><creatorcontrib>Fu, Jiangnan</creatorcontrib><creatorcontrib>Olkkonen, Vesa M.</creatorcontrib><creatorcontrib>Staels, Bart</creatorcontrib><creatorcontrib>Yan, Daoguang</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the American Heart Association</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Hongling</au><au>Zhong, Wenbin</au><au>Jiang, Yingliang</au><au>Fontaine, Coralie</au><au>Li, Shiqian</au><au>Fu, Jiangnan</au><au>Olkkonen, Vesa M.</au><au>Staels, Bart</au><au>Yan, Daoguang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased Atherosclerotic Lesions in LDL Receptor Deficient Mice With Hematopoietic Nuclear Receptor Rev‐erbα Knock‐ Down</atitle><jtitle>Journal of the American Heart Association</jtitle><addtitle>J Am Heart Assoc</addtitle><date>2013-08-20</date><risdate>2013</risdate><volume>2</volume><issue>4</issue><spage>e000235</spage><epage>n/a</epage><pages>e000235-n/a</pages><issn>2047-9980</issn><eissn>2047-9980</eissn><abstract>Background
Nuclear receptor Rev‐erbα plays important roles in circadian clock timing, lipid metabolism, adipogenesis, and vascular inflammation. However, the role of Rev‐erbα in atherosclerotic lesion development has not been assessed in vivo.
Methods and Results
The nuclear receptor Rev‐erbα was knocked down in mouse haematopoietic cells by means of shRNA‐lentiviral transduction, followed by bone marrow transplantation into LDL receptor knockout mice. The Rev‐erbα protein in peripheral macrophage was reduced by 70% as compared to control mice injected with nontargeting shRNA lentivirus‐transduced bone marrow. A significant increase in atherosclerotic lesions was observed around the aorta valves as well as upon en face aorta analysis of Rev‐erbα knock‐down bone marrow recipients (P<0.01) as compared to the control mice, while plasma cholesterol, phospholipid, and triacylglycerol levels were not affected. Overexpression of Rev‐erbα in bone marrow mononuclear cells decreased inflammatory M1 while increasing M2 macrophage markers, while Rev‐erbα knock down increased the macrophage inflammatory phenotype in vitro and in vivo. Furthermore, treatment of differentiating macrophages with the Rev‐erbα ligand heme promoted expression of antiinflammatory M2 markers.
Conclusions
These observations identify hematopoietic cell Rev‐erbα as a new modulator of atherogenesis in mice.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23963755</pmid><doi>10.1161/JAHA.113.000235</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley Online Library Open Access; PubMed Central |
| subjects | Animals Aorta - immunology Aorta - metabolism Aorta - pathology Aortic Diseases - genetics Aortic Diseases - immunology Aortic Diseases - metabolism Aortic Diseases - pathology atherosclerosis Atherosclerosis - genetics Atherosclerosis - immunology Atherosclerosis - metabolism Atherosclerosis - pathology Bone Marrow Transplantation Cells, Cultured Disease Models, Animal Gene Knockdown Techniques Genetic Vectors Genotype Inflammation Mediators - metabolism Lentivirus - genetics Lipids - blood Macrophage Activation macrophages Macrophages - immunology Macrophages - metabolism Macrophages - pathology Mice Mice, Inbred C57BL Mice, Knockout Nuclear Receptor Subfamily 1, Group D, Member 1 - deficiency Nuclear Receptor Subfamily 1, Group D, Member 1 - genetics Original Research Phenotype Receptors, LDL - deficiency Receptors, LDL - genetics Rev‐erbα RNA Interference Transduction, Genetic |
| title | Increased Atherosclerotic Lesions in LDL Receptor Deficient Mice With Hematopoietic Nuclear Receptor Rev‐erbα Knock‐ Down |
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