Increased expression of fatty acid binding protein 4 and leptin in resident macrophages characterises atherosclerotic plaque rupture
Abstract Objective Resident macrophages play an important role in atheromatous plaque rupture. The macrophage gene expression signature associated with plaque rupture is incompletely defined due to the complex cellular heterogeneity in the plaque. We aimed to characterise differential gene expressio...
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| Veröffentlicht in: | Atherosclerosis 2013-01, Vol.226 (1), p.74-81 |
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| creator | Lee, K Santibanez-Koref, M Polvikoski, T Birchall, D Mendelow, A.D Keavney, B |
| description | Abstract Objective Resident macrophages play an important role in atheromatous plaque rupture. The macrophage gene expression signature associated with plaque rupture is incompletely defined due to the complex cellular heterogeneity in the plaque. We aimed to characterise differential gene expression in resident plaque macrophages from ruptured and stable human atheromatous lesions. Methods and results We performed genome-wide expression analyses of isolated macrophage-rich regions of stable and ruptured human atherosclerotic plaques. Plaques present in carotid endarterectomy specimens were designated as stable or ruptured using clinical, radiological and histopathological criteria. Macrophage-rich regions were excised from 5 ruptured and 6 stable plaques by laser micro-dissection. Transcriptional profiling was performed using Affymetrix microarrays. The profiles were characteristic of activated macrophages. At a false discovery rate of 10%, 914 genes were differentially expressed between stable and ruptured plaques. The findings were confirmed in fourteen further stable and ruptured samples for a subset of eleven genes with the highest expression differences ( p |
| doi_str_mv | 10.1016/j.atherosclerosis.2012.09.037 |
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| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3566542</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0021915012006557</els_id><sourcerecordid>1273465732</sourcerecordid><originalsourceid>FETCH-LOGICAL-c608t-e6ccada4f13240b3c88fd02934ce0fd69ba358a9dd3f12298bb5dc1ed33af68a3</originalsourceid><addsrcrecordid>eNqNUk1vEzEUXCEQDYW_AL5U4pLgj_3wHqiEKiiVKnEoPVtv7beJw8ZebG9F7_xwvE2ISk9Ili3LM_PGb15RnDG6YpTVH7YrSBsMPuph3m1cccr4irYrKppnxYLJpl2yUpbPiwWlnC1bVtGT4lWMW0pp2TD5sjjhgnHeMr4ofl85HRAiGoK_xoAxWu-I70kPKd0T0NaQzjpj3ZqMwSe0jpQEnCEDjilf8sosa9AlsgMd_LiBNUaiNxBAJww25ttjz8lqMg7wc0ISpjFNAV8XL3oYIr45nKfF7ZfP3y--Lq-_XV5dfLpe6prKtMRaazBQ9kzwknZCS9kbyltRaqS9qdsORCWhNUb08_9k11VGMzRCQF9LEKfF-V53nLodGp09BxjUGOwOwr3yYNW_L85u1NrfKVHVdVXyLPD-IBB89h-T2tmocRjAoZ-iYrwRZV01YoZ-3ENzS2IM2B_LMKrmJNVWPUlSzUkq2qqcZOa_fez1yP4bXQacHQAQNQx9AKezxhFXS0GbB8_v9rgevIJ1zkPd3uRK1TwOsn0odblHYO79ncWgorboNBobUCdlvP1v0-dPlPRgnc32fuA9xq2fgssBK6Zi5qibeUDn-WSc0rrKffsD2uvqGQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1273465732</pqid></control><display><type>article</type><title>Increased expression of fatty acid binding protein 4 and leptin in resident macrophages characterises atherosclerotic plaque rupture</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Lee, K ; Santibanez-Koref, M ; Polvikoski, T ; Birchall, D ; Mendelow, A.D ; Keavney, B</creator><creatorcontrib>Lee, K ; Santibanez-Koref, M ; Polvikoski, T ; Birchall, D ; Mendelow, A.D ; Keavney, B</creatorcontrib><description>Abstract Objective Resident macrophages play an important role in atheromatous plaque rupture. The macrophage gene expression signature associated with plaque rupture is incompletely defined due to the complex cellular heterogeneity in the plaque. We aimed to characterise differential gene expression in resident plaque macrophages from ruptured and stable human atheromatous lesions. Methods and results We performed genome-wide expression analyses of isolated macrophage-rich regions of stable and ruptured human atherosclerotic plaques. Plaques present in carotid endarterectomy specimens were designated as stable or ruptured using clinical, radiological and histopathological criteria. Macrophage-rich regions were excised from 5 ruptured and 6 stable plaques by laser micro-dissection. Transcriptional profiling was performed using Affymetrix microarrays. The profiles were characteristic of activated macrophages. At a false discovery rate of 10%, 914 genes were differentially expressed between stable and ruptured plaques. The findings were confirmed in fourteen further stable and ruptured samples for a subset of eleven genes with the highest expression differences ( p < 0.05). Pathway analysis revealed that components of the PPAR/Adipocytokine signaling pathway were the most significantly upregulated in ruptured compared to stable plaques ( p = 5.4 × 10−7 ). Two key components of the pathway, fatty-acid binding-protein 4 (FABP4) and leptin, showed nine-fold ( p = 0.0086) and five-fold ( p = 0.0012) greater expression respectively in macrophages from ruptured plaques. Conclusions We found differences in gene expression signatures between macrophages isolated from stable and ruptured human atheromatous plaques. Our findings indicate the involvement of FABP4 and leptin in the progression of atherosclerosis and plaque rupture, and suggest that down-regulation of PPAR/adipocytokine signaling within plaques may have therapeutic potential.</description><identifier>ISSN: 0021-9150</identifier><identifier>EISSN: 1879-1484</identifier><identifier>DOI: 10.1016/j.atherosclerosis.2012.09.037</identifier><identifier>PMID: 23122912</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ireland Ltd</publisher><subject>Aged ; atherosclerosis ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cardiovascular ; Coronary heart disease ; fatty acid-binding proteins ; Fatty Acid-Binding Proteins - biosynthesis ; Fatty Acid-Binding Proteins - genetics ; Female ; Gene expression ; Gene Expression Regulation ; genes ; Genome-Wide Association Study ; Heart ; histopathology ; Humans ; Laser micro-dissection ; leptin ; Leptin - biosynthesis ; Leptin - genetics ; Macrophages ; Macrophages - metabolism ; Male ; Medical sciences ; Microarray ; microarray technology ; Plaque rupture ; Plaque, Atherosclerotic - complications ; Plaque, Atherosclerotic - genetics ; Plaque, Atherosclerotic - metabolism ; Rupture, Spontaneous ; signal transduction ; transcription (genetics)</subject><ispartof>Atherosclerosis, 2013-01, Vol.226 (1), p.74-81</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2012 Elsevier Ireland Ltd</rights><rights>2014 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.</rights><rights>2013 Elsevier Ireland Ltd. 2012 Elsevier Ireland Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c608t-e6ccada4f13240b3c88fd02934ce0fd69ba358a9dd3f12298bb5dc1ed33af68a3</citedby><cites>FETCH-LOGICAL-c608t-e6ccada4f13240b3c88fd02934ce0fd69ba358a9dd3f12298bb5dc1ed33af68a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0021915012006557$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26830742$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23122912$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, K</creatorcontrib><creatorcontrib>Santibanez-Koref, M</creatorcontrib><creatorcontrib>Polvikoski, T</creatorcontrib><creatorcontrib>Birchall, D</creatorcontrib><creatorcontrib>Mendelow, A.D</creatorcontrib><creatorcontrib>Keavney, B</creatorcontrib><title>Increased expression of fatty acid binding protein 4 and leptin in resident macrophages characterises atherosclerotic plaque rupture</title><title>Atherosclerosis</title><addtitle>Atherosclerosis</addtitle><description>Abstract Objective Resident macrophages play an important role in atheromatous plaque rupture. The macrophage gene expression signature associated with plaque rupture is incompletely defined due to the complex cellular heterogeneity in the plaque. We aimed to characterise differential gene expression in resident plaque macrophages from ruptured and stable human atheromatous lesions. Methods and results We performed genome-wide expression analyses of isolated macrophage-rich regions of stable and ruptured human atherosclerotic plaques. Plaques present in carotid endarterectomy specimens were designated as stable or ruptured using clinical, radiological and histopathological criteria. Macrophage-rich regions were excised from 5 ruptured and 6 stable plaques by laser micro-dissection. Transcriptional profiling was performed using Affymetrix microarrays. The profiles were characteristic of activated macrophages. At a false discovery rate of 10%, 914 genes were differentially expressed between stable and ruptured plaques. The findings were confirmed in fourteen further stable and ruptured samples for a subset of eleven genes with the highest expression differences ( p < 0.05). Pathway analysis revealed that components of the PPAR/Adipocytokine signaling pathway were the most significantly upregulated in ruptured compared to stable plaques ( p = 5.4 × 10−7 ). Two key components of the pathway, fatty-acid binding-protein 4 (FABP4) and leptin, showed nine-fold ( p = 0.0086) and five-fold ( p = 0.0012) greater expression respectively in macrophages from ruptured plaques. Conclusions We found differences in gene expression signatures between macrophages isolated from stable and ruptured human atheromatous plaques. Our findings indicate the involvement of FABP4 and leptin in the progression of atherosclerosis and plaque rupture, and suggest that down-regulation of PPAR/adipocytokine signaling within plaques may have therapeutic potential.</description><subject>Aged</subject><subject>atherosclerosis</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular</subject><subject>Coronary heart disease</subject><subject>fatty acid-binding proteins</subject><subject>Fatty Acid-Binding Proteins - biosynthesis</subject><subject>Fatty Acid-Binding Proteins - genetics</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>genes</subject><subject>Genome-Wide Association Study</subject><subject>Heart</subject><subject>histopathology</subject><subject>Humans</subject><subject>Laser micro-dissection</subject><subject>leptin</subject><subject>Leptin - biosynthesis</subject><subject>Leptin - genetics</subject><subject>Macrophages</subject><subject>Macrophages - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microarray</subject><subject>microarray technology</subject><subject>Plaque rupture</subject><subject>Plaque, Atherosclerotic - complications</subject><subject>Plaque, Atherosclerotic - genetics</subject><subject>Plaque, Atherosclerotic - metabolism</subject><subject>Rupture, Spontaneous</subject><subject>signal transduction</subject><subject>transcription (genetics)</subject><issn>0021-9150</issn><issn>1879-1484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUk1vEzEUXCEQDYW_AL5U4pLgj_3wHqiEKiiVKnEoPVtv7beJw8ZebG9F7_xwvE2ISk9Ili3LM_PGb15RnDG6YpTVH7YrSBsMPuph3m1cccr4irYrKppnxYLJpl2yUpbPiwWlnC1bVtGT4lWMW0pp2TD5sjjhgnHeMr4ofl85HRAiGoK_xoAxWu-I70kPKd0T0NaQzjpj3ZqMwSe0jpQEnCEDjilf8sosa9AlsgMd_LiBNUaiNxBAJww25ttjz8lqMg7wc0ISpjFNAV8XL3oYIr45nKfF7ZfP3y--Lq-_XV5dfLpe6prKtMRaazBQ9kzwknZCS9kbyltRaqS9qdsORCWhNUb08_9k11VGMzRCQF9LEKfF-V53nLodGp09BxjUGOwOwr3yYNW_L85u1NrfKVHVdVXyLPD-IBB89h-T2tmocRjAoZ-iYrwRZV01YoZ-3ENzS2IM2B_LMKrmJNVWPUlSzUkq2qqcZOa_fez1yP4bXQacHQAQNQx9AKezxhFXS0GbB8_v9rgevIJ1zkPd3uRK1TwOsn0odblHYO79ncWgorboNBobUCdlvP1v0-dPlPRgnc32fuA9xq2fgssBK6Zi5qibeUDn-WSc0rrKffsD2uvqGQ</recordid><startdate>20130101</startdate><enddate>20130101</enddate><creator>Lee, K</creator><creator>Santibanez-Koref, M</creator><creator>Polvikoski, T</creator><creator>Birchall, D</creator><creator>Mendelow, A.D</creator><creator>Keavney, B</creator><general>Elsevier Ireland Ltd</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><scope>IQODW</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>20130101</creationdate><title>Increased expression of fatty acid binding protein 4 and leptin in resident macrophages characterises atherosclerotic plaque rupture</title><author>Lee, K ; Santibanez-Koref, M ; Polvikoski, T ; Birchall, D ; Mendelow, A.D ; Keavney, B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c608t-e6ccada4f13240b3c88fd02934ce0fd69ba358a9dd3f12298bb5dc1ed33af68a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aged</topic><topic>atherosclerosis</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cardiovascular</topic><topic>Coronary heart disease</topic><topic>fatty acid-binding proteins</topic><topic>Fatty Acid-Binding Proteins - biosynthesis</topic><topic>Fatty Acid-Binding Proteins - genetics</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>genes</topic><topic>Genome-Wide Association Study</topic><topic>Heart</topic><topic>histopathology</topic><topic>Humans</topic><topic>Laser micro-dissection</topic><topic>leptin</topic><topic>Leptin - biosynthesis</topic><topic>Leptin - genetics</topic><topic>Macrophages</topic><topic>Macrophages - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microarray</topic><topic>microarray technology</topic><topic>Plaque rupture</topic><topic>Plaque, Atherosclerotic - complications</topic><topic>Plaque, Atherosclerotic - genetics</topic><topic>Plaque, Atherosclerotic - metabolism</topic><topic>Rupture, Spontaneous</topic><topic>signal transduction</topic><topic>transcription (genetics)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, K</creatorcontrib><creatorcontrib>Santibanez-Koref, M</creatorcontrib><creatorcontrib>Polvikoski, T</creatorcontrib><creatorcontrib>Birchall, D</creatorcontrib><creatorcontrib>Mendelow, A.D</creatorcontrib><creatorcontrib>Keavney, B</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><collection>Pascal-Francis</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>Atherosclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, K</au><au>Santibanez-Koref, M</au><au>Polvikoski, T</au><au>Birchall, D</au><au>Mendelow, A.D</au><au>Keavney, B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased expression of fatty acid binding protein 4 and leptin in resident macrophages characterises atherosclerotic plaque rupture</atitle><jtitle>Atherosclerosis</jtitle><addtitle>Atherosclerosis</addtitle><date>2013-01-01</date><risdate>2013</risdate><volume>226</volume><issue>1</issue><spage>74</spage><epage>81</epage><pages>74-81</pages><issn>0021-9150</issn><eissn>1879-1484</eissn><abstract>Abstract Objective Resident macrophages play an important role in atheromatous plaque rupture. The macrophage gene expression signature associated with plaque rupture is incompletely defined due to the complex cellular heterogeneity in the plaque. We aimed to characterise differential gene expression in resident plaque macrophages from ruptured and stable human atheromatous lesions. Methods and results We performed genome-wide expression analyses of isolated macrophage-rich regions of stable and ruptured human atherosclerotic plaques. Plaques present in carotid endarterectomy specimens were designated as stable or ruptured using clinical, radiological and histopathological criteria. Macrophage-rich regions were excised from 5 ruptured and 6 stable plaques by laser micro-dissection. Transcriptional profiling was performed using Affymetrix microarrays. The profiles were characteristic of activated macrophages. At a false discovery rate of 10%, 914 genes were differentially expressed between stable and ruptured plaques. The findings were confirmed in fourteen further stable and ruptured samples for a subset of eleven genes with the highest expression differences ( p < 0.05). Pathway analysis revealed that components of the PPAR/Adipocytokine signaling pathway were the most significantly upregulated in ruptured compared to stable plaques ( p = 5.4 × 10−7 ). Two key components of the pathway, fatty-acid binding-protein 4 (FABP4) and leptin, showed nine-fold ( p = 0.0086) and five-fold ( p = 0.0012) greater expression respectively in macrophages from ruptured plaques. Conclusions We found differences in gene expression signatures between macrophages isolated from stable and ruptured human atheromatous plaques. Our findings indicate the involvement of FABP4 and leptin in the progression of atherosclerosis and plaque rupture, and suggest that down-regulation of PPAR/adipocytokine signaling within plaques may have therapeutic potential.</abstract><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>23122912</pmid><doi>10.1016/j.atherosclerosis.2012.09.037</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged atherosclerosis Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cardiovascular Coronary heart disease fatty acid-binding proteins Fatty Acid-Binding Proteins - biosynthesis Fatty Acid-Binding Proteins - genetics Female Gene expression Gene Expression Regulation genes Genome-Wide Association Study Heart histopathology Humans Laser micro-dissection leptin Leptin - biosynthesis Leptin - genetics Macrophages Macrophages - metabolism Male Medical sciences Microarray microarray technology Plaque rupture Plaque, Atherosclerotic - complications Plaque, Atherosclerotic - genetics Plaque, Atherosclerotic - metabolism Rupture, Spontaneous signal transduction transcription (genetics) |
| title | Increased expression of fatty acid binding protein 4 and leptin in resident macrophages characterises atherosclerotic plaque rupture |
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