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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2005-10-28
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pubmed:abstractText |
Angiotensin II (Ang II) is a powerful accelerator of atherosclerosis. Herein, we describe a novel transcription mechanism through which Ang II inhibits macrophage expression of the ATP-binding cassette transporter A1 (ABCA1), a key regulator of reverse cholesterol transport. We demonstrate that chronic Ang II infusion substantially promotes macrophage infiltration, foam cell formation, and atherosclerosis in low-density lipoprotein receptor-deficient mice and significantly reduces ABCA1 expression in peripheral macrophages. Administration of the Ang II type 1 receptor blocker valsartan inhibited Ang II-induced ABCA1 mRNA repression, macrophage cholesterol accumulation, and atherosclerosis. Ang II treatment reduced ABCA1 promoter activity of in vitro cultured mouse peritoneal macrophages, inducing fos-related antigen 2 (Fra2) protein binding to an ABCA1 promoter E-box motif, a site known to negatively regulate macrophage ABCA1 transcription. Valsartan pretreatment blocked Fra2 binding to the ABCA1 promoter, and Fra2 small interfering RNA pretreatment attenuated Ang II-mediated ABCA1 transcriptional inhibition, confirming the role of Fra2 in this process. This new evidence suggests that Ang II, a well-known proinflammatory and pro-oxidative factor, alters macrophage cholesterol homeostasis by repressing ABCA1 to promote foam cell formation and atherosclerosis.
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pubmed:grant |
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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/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation...,
http://linkedlifedata.com/resource/pubmed/chemical/CD68 antigen, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Fos-Related Antigen-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1524-4571
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pubmed:author |
pubmed-author:BlaschkeFlorianF,
pubmed-author:BruemmerDennisD,
pubmed-author:CaglayanEvrenE,
pubmed-author:CollinsAlan RAR,
pubmed-author:DaleyWilliamW,
pubmed-author:DowW HWH,
pubmed-author:FishbeinMichael CMC,
pubmed-author:HigakiJitsuoJ,
pubmed-author:HsuehWilla AWA,
pubmed-author:LawRonald ERE,
pubmed-author:LyonChristopher JCJ,
pubmed-author:TakataYasunoriY,
pubmed-author:TangiralaRajendra KRK,
pubmed-author:VighB JBJ
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pubmed:issnType |
Electronic
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pubmed:day |
28
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pubmed:volume |
97
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
e88-96
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:16224068-ATP-Binding Cassette Transporters,
pubmed-meshheading:16224068-Angiotensin II,
pubmed-meshheading:16224068-Animals,
pubmed-meshheading:16224068-Antigens, CD,
pubmed-meshheading:16224068-Antigens, Differentiation, Myelomonocytic,
pubmed-meshheading:16224068-Atherosclerosis,
pubmed-meshheading:16224068-Cholesterol,
pubmed-meshheading:16224068-Fos-Related Antigen-2,
pubmed-meshheading:16224068-Macrophages,
pubmed-meshheading:16224068-Mice,
pubmed-meshheading:16224068-Promoter Regions, Genetic,
pubmed-meshheading:16224068-RNA, Messenger,
pubmed-meshheading:16224068-RNA, Small Interfering,
pubmed-meshheading:16224068-Receptors, LDL,
pubmed-meshheading:16224068-Repressor Proteins,
pubmed-meshheading:16224068-Transcription, Genetic
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pubmed:year |
2005
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pubmed:articleTitle |
Transcriptional repression of ATP-binding cassette transporter A1 gene in macrophages: a novel atherosclerotic effect of angiotensin II.
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pubmed:affiliation |
Division of Endocrinology, Diabetes, and Hypertension, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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