Coexistence of Foam Cells and Hypocholesterolemia in Mice Lacking the ABC Transporters Al and G1
Identifieur interne : 003353 ( PascalFrancis/Checkpoint ); précédent : 003352; suivant : 003354Coexistence of Foam Cells and Hypocholesterolemia in Mice Lacking the ABC Transporters Al and G1
Auteurs : Ruud Out [Pays-Bas] ; Wendy Jessup [Australie] ; Wilfried Le Goff [France] ; Menno Hoekstra [Pays-Bas] ; Ingrid C. Gelissen [Australie] ; YING ZHAO [Pays-Bas] ; Léonard Kritharides [Australie] ; Giovanna Chimini [France] ; Johan Kuiper [Pays-Bas] ; M. John Chapman [France] ; Thierry Huby [France] ; Theo J. C. Van Berkel [Pays-Bas] ; Miranda Van Eck [Pays-Bas]Source :
- Circulation research [ 0009-7330 ] ; 2008.
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Abstract
-The concept that macrophages can become foam cells as a result of a disturbed balance between the uptake of cholesterol from lipoproteins and cholesterol efflux is generally accepted. ABCA1 and ABCG1 are two cholesterol transporters that may act sequentially to remove cellular cholesterol, but currently their combined role in vivo is unknown. We report here that targeted disruption of both ABCA1 and ABCG1 in mice, despite severe plasma hypocholesterolemia, leads to massive lipid accumulation and foam cell formation of tissue macrophages. A complete ablation of cellular cholesterol efflux in vitro is observed, whereas in vivo macrophage-specific reverse cholesterol transport to the feces is markedly decreased. Despite the massive foam cell formation of tissue macrophages, no lipid accumulation was observed in the vascular wall, even in mice of 1 year old, indicating that the double knockout mice, possibly because of their hypocholesterolemia, lack the trigger to attract macrophages to the vessel wall. In conclusion, even under hypocholesterolemic conditions macrophages can be converted into foam cells, and ABCA1 and ABCG1 play an essential role in the prevention of foam cell formation.
Affiliations:
- Australie, France, Pays-Bas
- Nouvelle-Galles du Sud, Provence-Alpes-Côte d'Azur, Île-de-France
- Marseille, Paris, Sydney
- Université de la Méditerranée
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Pascal:08-0091348Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Coexistence of Foam Cells and Hypocholesterolemia in Mice Lacking the ABC Transporters Al and G1</title>
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<author><name sortKey="Van Berkel, Theo J C" sort="Van Berkel, Theo J C" uniqKey="Van Berkel T" first="Theo J. C." last="Van Berkel">Theo J. C. Van Berkel</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Biopharmaceutics 9, Leiden/Amsterdam Center for Drug Research, Leiden University</s1>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<wicri:noRegion>Division of Biopharmaceutics 9, Leiden/Amsterdam Center for Drug Research, Leiden University</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van Eck, Miranda" sort="Van Eck, Miranda" uniqKey="Van Eck M" first="Miranda" last="Van Eck">Miranda Van Eck</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Biopharmaceutics 9, Leiden/Amsterdam Center for Drug Research, Leiden University</s1>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<wicri:noRegion>Division of Biopharmaceutics 9, Leiden/Amsterdam Center for Drug Research, Leiden University</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Circulation research</title>
<title level="j" type="abbreviated">Circ. res.</title>
<idno type="ISSN">0009-7330</idno>
<imprint><date when="2008">2008</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Circulation research</title>
<title level="j" type="abbreviated">Circ. res.</title>
<idno type="ISSN">0009-7330</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>ABC transporter</term>
<term>Biological transport</term>
<term>Cholesterol</term>
<term>Circulatory system</term>
<term>Coexistence</term>
<term>Hypocholesterolemia</term>
<term>Lipids</term>
<term>Macrophage</term>
<term>Mammalia</term>
<term>Mouse</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Coexistence</term>
<term>Transporteur ABC</term>
<term>Cholestérol</term>
<term>Transport biologique</term>
<term>Macrophage</term>
<term>Appareil circulatoire</term>
<term>Mammalia</term>
<term>Hypocholestérolémie</term>
<term>Lipide</term>
<term>Souris</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">-The concept that macrophages can become foam cells as a result of a disturbed balance between the uptake of cholesterol from lipoproteins and cholesterol efflux is generally accepted. ABCA1 and ABCG1 are two cholesterol transporters that may act sequentially to remove cellular cholesterol, but currently their combined role in vivo is unknown. We report here that targeted disruption of both ABCA1 and ABCG1 in mice, despite severe plasma hypocholesterolemia, leads to massive lipid accumulation and foam cell formation of tissue macrophages. A complete ablation of cellular cholesterol efflux in vitro is observed, whereas in vivo macrophage-specific reverse cholesterol transport to the feces is markedly decreased. Despite the massive foam cell formation of tissue macrophages, no lipid accumulation was observed in the vascular wall, even in mice of 1 year old, indicating that the double knockout mice, possibly because of their hypocholesterolemia, lack the trigger to attract macrophages to the vessel wall. In conclusion, even under hypocholesterolemic conditions macrophages can be converted into foam cells, and ABCA1 and ABCG1 play an essential role in the prevention of foam cell formation.</div>
</front>
</TEI>
<inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0009-7330</s0>
</fA01>
<fA02 i1="01"><s0>CIRUAL</s0>
</fA02>
<fA03 i2="1"><s0>Circ. res.</s0>
</fA03>
<fA05><s2>102</s2>
</fA05>
<fA06><s2>1</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG"><s1>Coexistence of Foam Cells and Hypocholesterolemia in Mice Lacking the ABC Transporters Al and G1</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>OUT (Ruud)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>JESSUP (Wendy)</s1>
</fA11>
<fA11 i1="03" i2="1"><s1>LE GOFF (Wilfried)</s1>
</fA11>
<fA11 i1="04" i2="1"><s1>HOEKSTRA (Menno)</s1>
</fA11>
<fA11 i1="05" i2="1"><s1>GELISSEN (Ingrid C.)</s1>
</fA11>
<fA11 i1="06" i2="1"><s1>YING ZHAO</s1>
</fA11>
<fA11 i1="07" i2="1"><s1>KRITHARIDES (Léonard)</s1>
</fA11>
<fA11 i1="08" i2="1"><s1>CHIMINI (Giovanna)</s1>
</fA11>
<fA11 i1="09" i2="1"><s1>KUIPER (Johan)</s1>
</fA11>
<fA11 i1="10" i2="1"><s1>CHAPMAN (M. John)</s1>
</fA11>
<fA11 i1="11" i2="1"><s1>HUBY (Thierry)</s1>
</fA11>
<fA11 i1="12" i2="1"><s1>VAN BERKEL (Theo J. C.)</s1>
</fA11>
<fA11 i1="13" i2="1"><s1>VAN ECK (Miranda)</s1>
</fA11>
<fA14 i1="01"><s1>Division of Biopharmaceutics 9, Leiden/Amsterdam Center for Drug Research, Leiden University</s1>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>Centre for Vascular Research , School of Medical Sciences, University of New South Wales</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>7 aut.</sZ>
</fA14>
<fA14 i1="03"><s1>INSERM U551</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>3 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</fA14>
<fA14 i1="04"><s1>Université Pierre et Marie Curie-Paris6, UMR S551</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>3 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</fA14>
<fA14 i1="05"><s1>Centre d'Immunologie de Marseille Luminy , Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université de la Méditerranée</s1>
<s2>Marseille</s2>
<s3>FRA</s3>
<sZ>8 aut.</sZ>
</fA14>
<fA20><s1>113-120</s1>
</fA20>
<fA21><s1>2008</s1>
</fA21>
<fA23 i1="01"><s0>ENG</s0>
</fA23>
<fA43 i1="01"><s1>INIST</s1>
<s2>7216</s2>
<s5>354000162715540160</s5>
</fA43>
<fA44><s0>0000</s0>
<s1>© 2008 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>30 ref.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>08-0091348</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Circulation research</s0>
</fA64>
<fA66 i1="01"><s0>USA</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>-The concept that macrophages can become foam cells as a result of a disturbed balance between the uptake of cholesterol from lipoproteins and cholesterol efflux is generally accepted. ABCA1 and ABCG1 are two cholesterol transporters that may act sequentially to remove cellular cholesterol, but currently their combined role in vivo is unknown. We report here that targeted disruption of both ABCA1 and ABCG1 in mice, despite severe plasma hypocholesterolemia, leads to massive lipid accumulation and foam cell formation of tissue macrophages. A complete ablation of cellular cholesterol efflux in vitro is observed, whereas in vivo macrophage-specific reverse cholesterol transport to the feces is markedly decreased. Despite the massive foam cell formation of tissue macrophages, no lipid accumulation was observed in the vascular wall, even in mice of 1 year old, indicating that the double knockout mice, possibly because of their hypocholesterolemia, lack the trigger to attract macrophages to the vessel wall. In conclusion, even under hypocholesterolemic conditions macrophages can be converted into foam cells, and ABCA1 and ABCG1 play an essential role in the prevention of foam cell formation.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002A22</s0>
</fC02>
<fC02 i1="02" i2="X"><s0>002B22A</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Coexistence</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Coexistence</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Coexistencia</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Transporteur ABC</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>ABC transporter</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Transportador ABC</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Cholestérol</s0>
<s2>NK</s2>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Cholesterol</s0>
<s2>NK</s2>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Colesterol</s0>
<s2>NK</s2>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Transport biologique</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Biological transport</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Transporte biológico</s0>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Macrophage</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Macrophage</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Macrófago</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Appareil circulatoire</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Circulatory system</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Aparato circulatorio</s0>
<s5>06</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Mammalia</s0>
<s2>NS</s2>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Mammalia</s0>
<s2>NS</s2>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Mammalia</s0>
<s2>NS</s2>
<s5>07</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Hypocholestérolémie</s0>
<s5>09</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>Hypocholesterolemia</s0>
<s5>09</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Hipocolesterolemia</s0>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>Lipide</s0>
<s5>15</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG"><s0>Lipids</s0>
<s5>15</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA"><s0>Lípido</s0>
<s5>15</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE"><s0>Souris</s0>
<s5>54</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG"><s0>Mouse</s0>
<s5>54</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA"><s0>Ratón</s0>
<s5>54</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Maladie métabolique</s0>
<s5>20</s5>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Metabolic diseases</s0>
<s5>20</s5>
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<fC07 i1="02" i2="X" l="SPA"><s0>Metabolismo patología</s0>
<s5>20</s5>
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<fC07 i1="03" i2="X" l="FRE"><s0>Rodentia</s0>
<s2>NS</s2>
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<s2>NS</s2>
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<fC07 i1="03" i2="X" l="SPA"><s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fN21><s1>052</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
<affiliations><list><country><li>Australie</li>
<li>France</li>
<li>Pays-Bas</li>
</country>
<region><li>Nouvelle-Galles du Sud</li>
<li>Provence-Alpes-Côte d'Azur</li>
<li>Île-de-France</li>
</region>
<settlement><li>Marseille</li>
<li>Paris</li>
<li>Sydney</li>
</settlement>
<orgName><li>Université de la Méditerranée</li>
</orgName>
</list>
<tree><country name="Pays-Bas"><noRegion><name sortKey="Out, Ruud" sort="Out, Ruud" uniqKey="Out R" first="Ruud" last="Out">Ruud Out</name>
</noRegion>
<name sortKey="Hoekstra, Menno" sort="Hoekstra, Menno" uniqKey="Hoekstra M" first="Menno" last="Hoekstra">Menno Hoekstra</name>
<name sortKey="Kuiper, Johan" sort="Kuiper, Johan" uniqKey="Kuiper J" first="Johan" last="Kuiper">Johan Kuiper</name>
<name sortKey="Van Berkel, Theo J C" sort="Van Berkel, Theo J C" uniqKey="Van Berkel T" first="Theo J. C." last="Van Berkel">Theo J. C. Van Berkel</name>
<name sortKey="Van Eck, Miranda" sort="Van Eck, Miranda" uniqKey="Van Eck M" first="Miranda" last="Van Eck">Miranda Van Eck</name>
<name sortKey="Ying Zhao" sort="Ying Zhao" uniqKey="Ying Zhao" last="Ying Zhao">YING ZHAO</name>
</country>
<country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Jessup, Wendy" sort="Jessup, Wendy" uniqKey="Jessup W" first="Wendy" last="Jessup">Wendy Jessup</name>
</region>
<name sortKey="Gelissen, Ingrid C" sort="Gelissen, Ingrid C" uniqKey="Gelissen I" first="Ingrid C." last="Gelissen">Ingrid C. Gelissen</name>
<name sortKey="Kritharides, Leonard" sort="Kritharides, Leonard" uniqKey="Kritharides L" first="Léonard" last="Kritharides">Léonard Kritharides</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Le Goff, Wilfried" sort="Le Goff, Wilfried" uniqKey="Le Goff W" first="Wilfried" last="Le Goff">Wilfried Le Goff</name>
</region>
<name sortKey="Chapman, M John" sort="Chapman, M John" uniqKey="Chapman M" first="M. John" last="Chapman">M. John Chapman</name>
<name sortKey="Chapman, M John" sort="Chapman, M John" uniqKey="Chapman M" first="M. John" last="Chapman">M. John Chapman</name>
<name sortKey="Chimini, Giovanna" sort="Chimini, Giovanna" uniqKey="Chimini G" first="Giovanna" last="Chimini">Giovanna Chimini</name>
<name sortKey="Huby, Thierry" sort="Huby, Thierry" uniqKey="Huby T" first="Thierry" last="Huby">Thierry Huby</name>
<name sortKey="Huby, Thierry" sort="Huby, Thierry" uniqKey="Huby T" first="Thierry" last="Huby">Thierry Huby</name>
<name sortKey="Le Goff, Wilfried" sort="Le Goff, Wilfried" uniqKey="Le Goff W" first="Wilfried" last="Le Goff">Wilfried Le Goff</name>
</country>
</tree>
</affiliations>
</record>
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