Apolipoprotein CI aggravates atherosclerosis development in ApoE-knockout mice despite mediating cholesterol efflux from macrophages
Abstract Objective Apolipoprotein CI (apoCI) is expressed in the liver and in macrophages, and has several roles in lipid metabolism. Since macrophage apoCI expression might affect macrophage lipid homeostasis and atherosclerotic lesion development locally in the arterial wall, we investigated the e...
Gespeichert in:
| Veröffentlicht in: | Atherosclerosis 2007-11, Vol.195 (1), p.e9-e16 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e16 |
|---|---|
| container_issue | 1 |
| container_start_page | e9 |
| container_title | Atherosclerosis |
| container_volume | 195 |
| creator | Westerterp, Marit Van Eck, Miranda de Haan, Willeke Offerman, Erik H Van Berkel, Theo J.C Havekes, Louis M Rensen, Patrick C.N |
| description | Abstract Objective Apolipoprotein CI (apoCI) is expressed in the liver and in macrophages, and has several roles in lipid metabolism. Since macrophage apoCI expression might affect macrophage lipid homeostasis and atherosclerotic lesion development locally in the arterial wall, we investigated the effect of both systemic and macrophage apoCI on atherosclerotic lesion development. Methods and results To investigate whether physiological expression levels of apoCI affect atherosclerosis development, we first assessed the effect of systemic endogenous apoCI expression on atherosclerosis in apoe−/− apoc1+/+ as compared to apoe−/− apoc1−/− mice at 26 weeks of age. ApoCI expression increased plasma levels of triglycerides (TG) (+70%; P < 0.01) and cholesterol (+30%; P < 0.05), and increased the atherosclerotic lesion area in the aortic root (+87%; P < 0.05). Paradoxically, incubation of apoc1+/+ and apoc1−/− murine peritoneal macrophages with AcLDL (50 μg/mL; 48 h) revealed that macrophage apoCI decreased the accumulation of cellular cholesteryl esters (CE) relatively to free cholesterol (−22%; P < 0.05). Accordingly, exogenous human apoCI increased cholesterol efflux from AcLDL-laden wild-type macrophages, and to a similar extent as apoAI and apoE. To evaluate whether atherosclerosis development would be affected by macrophage apoCI expression in vivo , we assessed atherosclerotic lesion development at 16 weeks after transplantation of bone marrow from apoe−/− apoc1−/− or apoe−/− apoc1+/+ mice to apoe−/− apoc1+/+ mice. However, in the situation wherein the liver and adipose tissue still produce apoCI, macrophage apoCI expression did not affect plasma lipid levels or the atherosclerotic lesion area. Conclusions Systemic apoCI increases atherosclerosis, probably by inducing hyperlipidemia. Despite decreasing macrophage lipid accumulation in vitro , apoCI production by macrophages locally in the arterial wall does not affect atherosclerosis development in vivo. |
| doi_str_mv | 10.1016/j.atherosclerosis.2007.01.015 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68403480</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0021915007000561</els_id><sourcerecordid>68403480</sourcerecordid><originalsourceid>FETCH-LOGICAL-c423t-810e4b4f35699112fb3b55e09ab0db9d2867597769622e49a6be1a9676e089123</originalsourceid><addsrcrecordid>eNqNUsGO0zAQjRCILQu_gHyBW8rYSZz4ANKq2l1WWokDcLYcZ9K6deJgO9XunQ9fR62E1BPSyL6892bmzcuyTxTWFCj_sl-ruEPvgrbLa8KaAdRroKmqV9mKNrXIadmUr7MVAKO5oBVcZe9C2ANAWdPmbXZF64JB0xSr7O_N5KyZ3ORdRDOSzQNR261XRxUxkItWpMMjWjcNOEaSwIl7mx9Gpw9ujmQwGhMiTCYiGbAzKppxS_TOWQwxKViCfW_nJ9J7N5BBae-mndpieJ-96ZUN-OH8X2e_725_bb7njz_uHzY3j7kuWRHzhgKWbdkXFReCUta3RVtVCEK10LWiYw2vK1HXXHDGsBSKt0iV4DVHaARlxXX2-aSbtv0zp6HkYIJGa9WIbg6SNyUUZQMJ-PUETCOG4LGXkzeD8s-SglzOIPfywhu5nEECTVUl_sdzo7lNTvxjn31PgPsTANO6R4NeBm1w1Mk1jzrKzpn_bvXtQklbMxqt7AGfMezd7MfkqaQyMAny55KJJRJQpzhUnBYvGbC60g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>68403480</pqid></control><display><type>article</type><title>Apolipoprotein CI aggravates atherosclerosis development in ApoE-knockout mice despite mediating cholesterol efflux from macrophages</title><source>MEDLINE</source><source>ScienceDirect Freedom Collection (Elsevier)</source><creator>Westerterp, Marit ; Van Eck, Miranda ; de Haan, Willeke ; Offerman, Erik H ; Van Berkel, Theo J.C ; Havekes, Louis M ; Rensen, Patrick C.N</creator><creatorcontrib>Westerterp, Marit ; Van Eck, Miranda ; de Haan, Willeke ; Offerman, Erik H ; Van Berkel, Theo J.C ; Havekes, Louis M ; Rensen, Patrick C.N</creatorcontrib><description>Abstract Objective Apolipoprotein CI (apoCI) is expressed in the liver and in macrophages, and has several roles in lipid metabolism. Since macrophage apoCI expression might affect macrophage lipid homeostasis and atherosclerotic lesion development locally in the arterial wall, we investigated the effect of both systemic and macrophage apoCI on atherosclerotic lesion development. Methods and results To investigate whether physiological expression levels of apoCI affect atherosclerosis development, we first assessed the effect of systemic endogenous apoCI expression on atherosclerosis in apoe−/− apoc1+/+ as compared to apoe−/− apoc1−/− mice at 26 weeks of age. ApoCI expression increased plasma levels of triglycerides (TG) (+70%; P < 0.01) and cholesterol (+30%; P < 0.05), and increased the atherosclerotic lesion area in the aortic root (+87%; P < 0.05). Paradoxically, incubation of apoc1+/+ and apoc1−/− murine peritoneal macrophages with AcLDL (50 μg/mL; 48 h) revealed that macrophage apoCI decreased the accumulation of cellular cholesteryl esters (CE) relatively to free cholesterol (−22%; P < 0.05). Accordingly, exogenous human apoCI increased cholesterol efflux from AcLDL-laden wild-type macrophages, and to a similar extent as apoAI and apoE. To evaluate whether atherosclerosis development would be affected by macrophage apoCI expression in vivo , we assessed atherosclerotic lesion development at 16 weeks after transplantation of bone marrow from apoe−/− apoc1−/− or apoe−/− apoc1+/+ mice to apoe−/− apoc1+/+ mice. However, in the situation wherein the liver and adipose tissue still produce apoCI, macrophage apoCI expression did not affect plasma lipid levels or the atherosclerotic lesion area. Conclusions Systemic apoCI increases atherosclerosis, probably by inducing hyperlipidemia. Despite decreasing macrophage lipid accumulation in vitro , apoCI production by macrophages locally in the arterial wall does not affect atherosclerosis development in vivo.</description><identifier>ISSN: 0021-9150</identifier><identifier>EISSN: 1879-1484</identifier><identifier>DOI: 10.1016/j.atherosclerosis.2007.01.015</identifier><identifier>PMID: 17320883</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Animals ; ApoCI ; Apolipoprotein C-I - metabolism ; Apolipoprotein C-I - physiology ; Apolipoproteins E - metabolism ; Atherosclerosis ; Bone Marrow Cells - metabolism ; Bone Marrow Transplantation ; Cardiovascular ; Cholesterol - metabolism ; Cholesterol efflux ; Female ; Gene Expression Regulation ; Hyperlipidemia ; Liver - metabolism ; Macrophages ; Macrophages - metabolism ; Male ; Mice ; Mice, Knockout ; Mice, Transgenic ; Transgenic mice</subject><ispartof>Atherosclerosis, 2007-11, Vol.195 (1), p.e9-e16</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2007 Elsevier Ireland Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-810e4b4f35699112fb3b55e09ab0db9d2867597769622e49a6be1a9676e089123</citedby><cites>FETCH-LOGICAL-c423t-810e4b4f35699112fb3b55e09ab0db9d2867597769622e49a6be1a9676e089123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.atherosclerosis.2007.01.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17320883$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Westerterp, Marit</creatorcontrib><creatorcontrib>Van Eck, Miranda</creatorcontrib><creatorcontrib>de Haan, Willeke</creatorcontrib><creatorcontrib>Offerman, Erik H</creatorcontrib><creatorcontrib>Van Berkel, Theo J.C</creatorcontrib><creatorcontrib>Havekes, Louis M</creatorcontrib><creatorcontrib>Rensen, Patrick C.N</creatorcontrib><title>Apolipoprotein CI aggravates atherosclerosis development in ApoE-knockout mice despite mediating cholesterol efflux from macrophages</title><title>Atherosclerosis</title><addtitle>Atherosclerosis</addtitle><description>Abstract Objective Apolipoprotein CI (apoCI) is expressed in the liver and in macrophages, and has several roles in lipid metabolism. Since macrophage apoCI expression might affect macrophage lipid homeostasis and atherosclerotic lesion development locally in the arterial wall, we investigated the effect of both systemic and macrophage apoCI on atherosclerotic lesion development. Methods and results To investigate whether physiological expression levels of apoCI affect atherosclerosis development, we first assessed the effect of systemic endogenous apoCI expression on atherosclerosis in apoe−/− apoc1+/+ as compared to apoe−/− apoc1−/− mice at 26 weeks of age. ApoCI expression increased plasma levels of triglycerides (TG) (+70%; P < 0.01) and cholesterol (+30%; P < 0.05), and increased the atherosclerotic lesion area in the aortic root (+87%; P < 0.05). Paradoxically, incubation of apoc1+/+ and apoc1−/− murine peritoneal macrophages with AcLDL (50 μg/mL; 48 h) revealed that macrophage apoCI decreased the accumulation of cellular cholesteryl esters (CE) relatively to free cholesterol (−22%; P < 0.05). Accordingly, exogenous human apoCI increased cholesterol efflux from AcLDL-laden wild-type macrophages, and to a similar extent as apoAI and apoE. To evaluate whether atherosclerosis development would be affected by macrophage apoCI expression in vivo , we assessed atherosclerotic lesion development at 16 weeks after transplantation of bone marrow from apoe−/− apoc1−/− or apoe−/− apoc1+/+ mice to apoe−/− apoc1+/+ mice. However, in the situation wherein the liver and adipose tissue still produce apoCI, macrophage apoCI expression did not affect plasma lipid levels or the atherosclerotic lesion area. Conclusions Systemic apoCI increases atherosclerosis, probably by inducing hyperlipidemia. Despite decreasing macrophage lipid accumulation in vitro , apoCI production by macrophages locally in the arterial wall does not affect atherosclerosis development in vivo.</description><subject>Animals</subject><subject>ApoCI</subject><subject>Apolipoprotein C-I - metabolism</subject><subject>Apolipoprotein C-I - physiology</subject><subject>Apolipoproteins E - metabolism</subject><subject>Atherosclerosis</subject><subject>Bone Marrow Cells - metabolism</subject><subject>Bone Marrow Transplantation</subject><subject>Cardiovascular</subject><subject>Cholesterol - metabolism</subject><subject>Cholesterol efflux</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Hyperlipidemia</subject><subject>Liver - metabolism</subject><subject>Macrophages</subject><subject>Macrophages - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Transgenic mice</subject><issn>0021-9150</issn><issn>1879-1484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUsGO0zAQjRCILQu_gHyBW8rYSZz4ANKq2l1WWokDcLYcZ9K6deJgO9XunQ9fR62E1BPSyL6892bmzcuyTxTWFCj_sl-ruEPvgrbLa8KaAdRroKmqV9mKNrXIadmUr7MVAKO5oBVcZe9C2ANAWdPmbXZF64JB0xSr7O_N5KyZ3ORdRDOSzQNR261XRxUxkItWpMMjWjcNOEaSwIl7mx9Gpw9ujmQwGhMiTCYiGbAzKppxS_TOWQwxKViCfW_nJ9J7N5BBae-mndpieJ-96ZUN-OH8X2e_725_bb7njz_uHzY3j7kuWRHzhgKWbdkXFReCUta3RVtVCEK10LWiYw2vK1HXXHDGsBSKt0iV4DVHaARlxXX2-aSbtv0zp6HkYIJGa9WIbg6SNyUUZQMJ-PUETCOG4LGXkzeD8s-SglzOIPfywhu5nEECTVUl_sdzo7lNTvxjn31PgPsTANO6R4NeBm1w1Mk1jzrKzpn_bvXtQklbMxqt7AGfMezd7MfkqaQyMAny55KJJRJQpzhUnBYvGbC60g</recordid><startdate>200711</startdate><enddate>200711</enddate><creator>Westerterp, Marit</creator><creator>Van Eck, Miranda</creator><creator>de Haan, Willeke</creator><creator>Offerman, Erik H</creator><creator>Van Berkel, Theo J.C</creator><creator>Havekes, Louis M</creator><creator>Rensen, Patrick C.N</creator><general>Elsevier Ireland Ltd</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>7X8</scope></search><sort><creationdate>200711</creationdate><title>Apolipoprotein CI aggravates atherosclerosis development in ApoE-knockout mice despite mediating cholesterol efflux from macrophages</title><author>Westerterp, Marit ; Van Eck, Miranda ; de Haan, Willeke ; Offerman, Erik H ; Van Berkel, Theo J.C ; Havekes, Louis M ; Rensen, Patrick C.N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-810e4b4f35699112fb3b55e09ab0db9d2867597769622e49a6be1a9676e089123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>ApoCI</topic><topic>Apolipoprotein C-I - metabolism</topic><topic>Apolipoprotein C-I - physiology</topic><topic>Apolipoproteins E - metabolism</topic><topic>Atherosclerosis</topic><topic>Bone Marrow Cells - metabolism</topic><topic>Bone Marrow Transplantation</topic><topic>Cardiovascular</topic><topic>Cholesterol - metabolism</topic><topic>Cholesterol efflux</topic><topic>Female</topic><topic>Gene Expression Regulation</topic><topic>Hyperlipidemia</topic><topic>Liver - metabolism</topic><topic>Macrophages</topic><topic>Macrophages - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mice, Transgenic</topic><topic>Transgenic mice</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Westerterp, Marit</creatorcontrib><creatorcontrib>Van Eck, Miranda</creatorcontrib><creatorcontrib>de Haan, Willeke</creatorcontrib><creatorcontrib>Offerman, Erik H</creatorcontrib><creatorcontrib>Van Berkel, Theo J.C</creatorcontrib><creatorcontrib>Havekes, Louis M</creatorcontrib><creatorcontrib>Rensen, Patrick C.N</creatorcontrib><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><jtitle>Atherosclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Westerterp, Marit</au><au>Van Eck, Miranda</au><au>de Haan, Willeke</au><au>Offerman, Erik H</au><au>Van Berkel, Theo J.C</au><au>Havekes, Louis M</au><au>Rensen, Patrick C.N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Apolipoprotein CI aggravates atherosclerosis development in ApoE-knockout mice despite mediating cholesterol efflux from macrophages</atitle><jtitle>Atherosclerosis</jtitle><addtitle>Atherosclerosis</addtitle><date>2007-11</date><risdate>2007</risdate><volume>195</volume><issue>1</issue><spage>e9</spage><epage>e16</epage><pages>e9-e16</pages><issn>0021-9150</issn><eissn>1879-1484</eissn><abstract>Abstract Objective Apolipoprotein CI (apoCI) is expressed in the liver and in macrophages, and has several roles in lipid metabolism. Since macrophage apoCI expression might affect macrophage lipid homeostasis and atherosclerotic lesion development locally in the arterial wall, we investigated the effect of both systemic and macrophage apoCI on atherosclerotic lesion development. Methods and results To investigate whether physiological expression levels of apoCI affect atherosclerosis development, we first assessed the effect of systemic endogenous apoCI expression on atherosclerosis in apoe−/− apoc1+/+ as compared to apoe−/− apoc1−/− mice at 26 weeks of age. ApoCI expression increased plasma levels of triglycerides (TG) (+70%; P < 0.01) and cholesterol (+30%; P < 0.05), and increased the atherosclerotic lesion area in the aortic root (+87%; P < 0.05). Paradoxically, incubation of apoc1+/+ and apoc1−/− murine peritoneal macrophages with AcLDL (50 μg/mL; 48 h) revealed that macrophage apoCI decreased the accumulation of cellular cholesteryl esters (CE) relatively to free cholesterol (−22%; P < 0.05). Accordingly, exogenous human apoCI increased cholesterol efflux from AcLDL-laden wild-type macrophages, and to a similar extent as apoAI and apoE. To evaluate whether atherosclerosis development would be affected by macrophage apoCI expression in vivo , we assessed atherosclerotic lesion development at 16 weeks after transplantation of bone marrow from apoe−/− apoc1−/− or apoe−/− apoc1+/+ mice to apoe−/− apoc1+/+ mice. However, in the situation wherein the liver and adipose tissue still produce apoCI, macrophage apoCI expression did not affect plasma lipid levels or the atherosclerotic lesion area. Conclusions Systemic apoCI increases atherosclerosis, probably by inducing hyperlipidemia. Despite decreasing macrophage lipid accumulation in vitro , apoCI production by macrophages locally in the arterial wall does not affect atherosclerosis development in vivo.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>17320883</pmid><doi>10.1016/j.atherosclerosis.2007.01.015</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9150 |
| ispartof | Atherosclerosis, 2007-11, Vol.195 (1), p.e9-e16 |
| issn | 0021-9150 1879-1484 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68403480 |
| source | MEDLINE; ScienceDirect Freedom Collection (Elsevier) |
| subjects | Animals ApoCI Apolipoprotein C-I - metabolism Apolipoprotein C-I - physiology Apolipoproteins E - metabolism Atherosclerosis Bone Marrow Cells - metabolism Bone Marrow Transplantation Cardiovascular Cholesterol - metabolism Cholesterol efflux Female Gene Expression Regulation Hyperlipidemia Liver - metabolism Macrophages Macrophages - metabolism Male Mice Mice, Knockout Mice, Transgenic Transgenic mice |
| title | Apolipoprotein CI aggravates atherosclerosis development in ApoE-knockout mice despite mediating cholesterol efflux from macrophages |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T06%3A31%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Apolipoprotein%20CI%20aggravates%20atherosclerosis%20development%20in%20ApoE-knockout%20mice%20despite%20mediating%20cholesterol%20efflux%20from%20macrophages&rft.jtitle=Atherosclerosis&rft.au=Westerterp,%20Marit&rft.date=2007-11&rft.volume=195&rft.issue=1&rft.spage=e9&rft.epage=e16&rft.pages=e9-e16&rft.issn=0021-9150&rft.eissn=1879-1484&rft_id=info:doi/10.1016/j.atherosclerosis.2007.01.015&rft_dat=%3Cproquest_cross%3E68403480%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=68403480&rft_id=info:pmid/17320883&rft_els_id=1_s2_0_S0021915007000561&rfr_iscdi=true |