Hypocholesterolemia, foam cell accumulation, but no atherosclerosis in mice lacking ABC-transporter A1 and scavenger receptor BI
Identifieur interne : 006A28 ( Main/Exploration ); précédent : 006A27; suivant : 006A29Hypocholesterolemia, foam cell accumulation, but no atherosclerosis in mice lacking ABC-transporter A1 and scavenger receptor BI
Auteurs : YING ZHAO [Pays-Bas] ; Marieke Pennings [Pays-Bas] ; Carlos Lj. Vrins [Pays-Bas] ; Laura Calpe-Berdiel [Pays-Bas] ; Menno Hoekstra [Pays-Bas] ; J. Kar Kruijt [Pays-Bas] ; Roelof Ottenhoff [Pays-Bas] ; Reeni B. Hildebrand [Pays-Bas] ; Ronald Van Der Sluis [Pays-Bas] ; Wendy Jessup [Australie] ; Wilfried Le Goff [France] ; M. John Chapman [France] ; Thierry Huby [France] ; Albert K. Groen [Pays-Bas] ; Theo J. C. Van Berkel [Pays-Bas] ; Miranda Van Eck [Pays-Bas]Source :
- Atherosclerosis [ 0021-9150 ] ; 2011.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
High-density lipoprotein (HDL) mediated reverse cholesterol transport (RCT) is regarded to be crucial for prevention of foam cell formation and atherosclerosis. ABC-transporter A1 (ABCA1) and scavenger receptor BI (SR-BI) are involved in the biogenesis of HDL and the selective delivery of HDL cholesterol to the liver, respectively. In the present study, we phenotypically characterized mice lacking these two proteins essential for HDL metabolism. ABCA1 × SR-BI double knockout (dKO) mice showed severe hypocholesterolemia mainly due to HDL loss, despite a 90% reduction of HDL cholesterol uptake by liver. VLDL production was increased in dKO mice. However, non-HDL cholesterol levels were reduced, probably due to enhanced clearance via LRP1. Hepatobiliary cholesterol transport and fecal sterol excretion were not impaired in dKO mice. In contrast, the macrophage RCT in dKO mice was markedly impaired as compared to WT mice, associated with the accumulation of macrophage foam cells in the lung and Peyer's patches. Strikingly, no atherosclerotic lesion formation was observed in dKO mice. In conclusion, both ABCA1 and SR-BI are essential for maintaining a properly functioning HDL-mediated macrophage RCT, while the potential anti-atherosclerotic functions of ABCA1 and SR-BI are not evident in dKO mice due to the absence of pro-atherogenic lipoproteins.
Affiliations:
- Australie, France, Pays-Bas
- Groningue (province), Hollande-Septentrionale, Nouvelle-Galles du Sud, Île-de-France
- Amsterdam, Groningue, Paris, Sydney
Links toward previous steps (curation, corpus...)
- to stream PascalFrancis, to step Corpus: 001906
- to stream PascalFrancis, to step Curation: 004650
- to stream PascalFrancis, to step Checkpoint: 001A12
- to stream Main, to step Merge: 006E63
- to stream Main, to step Curation: 006A28
Le document en format XML
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<author><name sortKey="Van Der Sluis, Ronald" sort="Van Der Sluis, Ronald" uniqKey="Van Der Sluis R" first="Ronald" last="Van Der Sluis">Ronald Van Der Sluis</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Einsteinweg 55</s1>
<s2>2333 CC Leiden</s2>
<s3>NLD</s3>
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<sZ>16 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<wicri:noRegion>2333 CC Leiden</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jessup, Wendy" sort="Jessup, Wendy" uniqKey="Jessup W" first="Wendy" last="Jessup">Wendy Jessup</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Centre for Vascular Research, University of New South Wales</s1>
<s2>Sydney</s2>
<s3>AUS</s3>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<placeName><settlement type="city">Sydney</settlement>
<region type="état">Nouvelle-Galles du Sud</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Le Goff, Wilfried" sort="Le Goff, Wilfried" uniqKey="Le Goff W" first="Wilfried" last="Le Goff">Wilfried Le Goff</name>
<affiliation wicri:level="3"><inist:fA14 i1="04"><s1>INSERM, UMRS939</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>UPMC Univ Paris 06, UMRS939 Paris</s1>
<s3>FRA</s3>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>UMRS939 Paris</wicri:noRegion>
<wicri:noRegion>UPMC Univ Paris 06, UMRS939 Paris</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chapman, M John" sort="Chapman, M John" uniqKey="Chapman M" first="M. John" last="Chapman">M. John Chapman</name>
<affiliation wicri:level="3"><inist:fA14 i1="04"><s1>INSERM, UMRS939</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>UPMC Univ Paris 06, UMRS939 Paris</s1>
<s3>FRA</s3>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>UMRS939 Paris</wicri:noRegion>
<wicri:noRegion>UPMC Univ Paris 06, UMRS939 Paris</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Huby, Thierry" sort="Huby, Thierry" uniqKey="Huby T" first="Thierry" last="Huby">Thierry Huby</name>
<affiliation wicri:level="3"><inist:fA14 i1="04"><s1>INSERM, UMRS939</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>UPMC Univ Paris 06, UMRS939 Paris</s1>
<s3>FRA</s3>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>UMRS939 Paris</wicri:noRegion>
<wicri:noRegion>UPMC Univ Paris 06, UMRS939 Paris</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Groen, Albert K" sort="Groen, Albert K" uniqKey="Groen A" first="Albert K." last="Groen">Albert K. Groen</name>
<affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Department of Pediatrics, University Medical Center Groningen</s1>
<s2>Groningen</s2>
<s3>NLD</s3>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<placeName><settlement type="city">Groningue</settlement>
<region nuts="2" type="province">Groningue (province)</region>
</placeName>
</affiliation>
</author>
<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, Leiden/Amsterdam Center for Drug Research, Leiden University, Einsteinweg 55</s1>
<s2>2333 CC Leiden</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>15 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<wicri:noRegion>2333 CC Leiden</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, Leiden/Amsterdam Center for Drug Research, Leiden University, Einsteinweg 55</s1>
<s2>2333 CC Leiden</s2>
<s3>NLD</s3>
<sZ>1 aut.</sZ>
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<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
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<sZ>9 aut.</sZ>
<sZ>15 aut.</sZ>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>Pays-Bas</country>
<wicri:noRegion>2333 CC Leiden</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Atherosclerosis</title>
<title level="j" type="abbreviated">Atherosclerosis</title>
<idno type="ISSN">0021-9150</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Atherosclerosis</title>
<title level="j" type="abbreviated">Atherosclerosis</title>
<idno type="ISSN">0021-9150</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal</term>
<term>Atherosclerosis</term>
<term>Cardiovascular disease</term>
<term>Cholesterol</term>
<term>Foam cell</term>
<term>Hypocholesterolemia</term>
<term>Lipids</term>
<term>Mouse</term>
<term>Transport</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Hypocholestérolémie</term>
<term>Athérosclérose</term>
<term>Pathologie de l'appareil circulatoire</term>
<term>Cellule spumeuse</term>
<term>Animal</term>
<term>Souris</term>
<term>Cholestérol</term>
<term>Transport</term>
<term>Lipide</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">High-density lipoprotein (HDL) mediated reverse cholesterol transport (RCT) is regarded to be crucial for prevention of foam cell formation and atherosclerosis. ABC-transporter A1 (ABCA1) and scavenger receptor BI (SR-BI) are involved in the biogenesis of HDL and the selective delivery of HDL cholesterol to the liver, respectively. In the present study, we phenotypically characterized mice lacking these two proteins essential for HDL metabolism. ABCA1 × SR-BI double knockout (dKO) mice showed severe hypocholesterolemia mainly due to HDL loss, despite a 90% reduction of HDL cholesterol uptake by liver. VLDL production was increased in dKO mice. However, non-HDL cholesterol levels were reduced, probably due to enhanced clearance via LRP1. Hepatobiliary cholesterol transport and fecal sterol excretion were not impaired in dKO mice. In contrast, the macrophage RCT in dKO mice was markedly impaired as compared to WT mice, associated with the accumulation of macrophage foam cells in the lung and Peyer's patches. Strikingly, no atherosclerotic lesion formation was observed in dKO mice. In conclusion, both ABCA1 and SR-BI are essential for maintaining a properly functioning HDL-mediated macrophage RCT, while the potential anti-atherosclerotic functions of ABCA1 and SR-BI are not evident in dKO mice due to the absence of pro-atherogenic lipoproteins.</div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>France</li>
<li>Pays-Bas</li>
</country>
<region><li>Groningue (province)</li>
<li>Hollande-Septentrionale</li>
<li>Nouvelle-Galles du Sud</li>
<li>Île-de-France</li>
</region>
<settlement><li>Amsterdam</li>
<li>Groningue</li>
<li>Paris</li>
<li>Sydney</li>
</settlement>
</list>
<tree><country name="Pays-Bas"><noRegion><name sortKey="Ying Zhao" sort="Ying Zhao" uniqKey="Ying Zhao" last="Ying Zhao">YING ZHAO</name>
</noRegion>
<name sortKey="Calpe Berdiel, Laura" sort="Calpe Berdiel, Laura" uniqKey="Calpe Berdiel L" first="Laura" last="Calpe-Berdiel">Laura Calpe-Berdiel</name>
<name sortKey="Groen, Albert K" sort="Groen, Albert K" uniqKey="Groen A" first="Albert K." last="Groen">Albert K. Groen</name>
<name sortKey="Hildebrand, Reeni B" sort="Hildebrand, Reeni B" uniqKey="Hildebrand R" first="Reeni B." last="Hildebrand">Reeni B. Hildebrand</name>
<name sortKey="Hoekstra, Menno" sort="Hoekstra, Menno" uniqKey="Hoekstra M" first="Menno" last="Hoekstra">Menno Hoekstra</name>
<name sortKey="Kar Kruijt, J" sort="Kar Kruijt, J" uniqKey="Kar Kruijt J" first="J." last="Kar Kruijt">J. Kar Kruijt</name>
<name sortKey="Ottenhoff, Roelof" sort="Ottenhoff, Roelof" uniqKey="Ottenhoff R" first="Roelof" last="Ottenhoff">Roelof Ottenhoff</name>
<name sortKey="Pennings, Marieke" sort="Pennings, Marieke" uniqKey="Pennings M" first="Marieke" last="Pennings">Marieke Pennings</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 Der Sluis, Ronald" sort="Van Der Sluis, Ronald" uniqKey="Van Der Sluis R" first="Ronald" last="Van Der Sluis">Ronald Van Der Sluis</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="Vrins, Carlos Lj" sort="Vrins, Carlos Lj" uniqKey="Vrins C" first="Carlos Lj." last="Vrins">Carlos Lj. Vrins</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>
</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="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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