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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2007-5-18
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pubmed:abstractText |
Accumulation of lipid-laden macrophages is a hallmark of atherosclerosis. The relevance of the key transcription factor nuclear factor kappaB (NF-kappaB) for macrophage-derived foam-cell formation has not been unequivocally resolved. Transgenic mice lines were generated in which NF-kappaB activation is specifically inhibited in macrophages by overexpressing a trans-dominant, non-degradable form of IkappaBalpha (IkappaBalpha (32A/36A)) under control of the macrophage-specific SR-A promoter. Alanine substitution of serines 32 and 36 prevents degradation and retains the inactive NF-kappaB/IkappaBalpha (32A/36A) complex in the cytoplasm. Similarly, stable human THP1 monocytic cell lines were generated with integrated copies of IkappaBalpha (32A/36A) cDNA. Upon treatment with oxidized low-density lipoprotein (ox-LDL), murine peritoneal macrophages from transgenic IkappaBalpha (32A/36A) mice, as well as THP1/IkappaBalpha (32A/36A) clones, display decreased lipid loading after differentiation into macrophages. This is accompanied by increased expression of the transcription factors PPARgamma and LXRalpha as well as of the major cholesterol-efflux transporter ABCA1. Paradoxically, mRNA expression of the 'lipid-uptake' receptor CD36 is also increased. Since the net result of these changes is reduction of foam-cell formation, it is proposed that under specific inhibition of NF-kappaB activation, ABCA1-mediated cholesterol efflux prevails over CD36-mediated lipid influx.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATP binding cassette transporter 1,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD36,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Orphan Nuclear Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Scavenger Receptors, Class A,
http://linkedlifedata.com/resource/pubmed/chemical/liver X receptor,
http://linkedlifedata.com/resource/pubmed/chemical/oxidized low density lipoprotein
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9150
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
192
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
283-90
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16938301-ATP-Binding Cassette Transporters,
pubmed-meshheading:16938301-Animals,
pubmed-meshheading:16938301-Antigens, CD36,
pubmed-meshheading:16938301-Cell Line,
pubmed-meshheading:16938301-DNA-Binding Proteins,
pubmed-meshheading:16938301-Foam Cells,
pubmed-meshheading:16938301-Humans,
pubmed-meshheading:16938301-I-kappa B Proteins,
pubmed-meshheading:16938301-Lipoproteins, LDL,
pubmed-meshheading:16938301-Macrophages,
pubmed-meshheading:16938301-Mice,
pubmed-meshheading:16938301-Mice, Inbred C57BL,
pubmed-meshheading:16938301-NF-kappa B,
pubmed-meshheading:16938301-Orphan Nuclear Receptors,
pubmed-meshheading:16938301-PPAR gamma,
pubmed-meshheading:16938301-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:16938301-Scavenger Receptors, Class A
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pubmed:year |
2007
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pubmed:articleTitle |
Macrophage-specific inhibition of NF-kappaB activation reduces foam-cell formation.
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pubmed:affiliation |
Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. v.ferreira@amc.uva.nl <v.ferreira@amc.uva.nl>
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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