| P2Y13 receptor is critical for reverse cholesterol transport. | |
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MedLine Citation:
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PMID: 20830789 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A major atheroprotective functionality of high-density lipoproteins (HDLs) is to promote "reverse cholesterol transport" (RCT). In this process, HDLs mediate the efflux and transport of cholesterol from peripheral cells and its subsequent transport to the liver for further metabolism and biliary excretion. We have previously demonstrated in cultured hepatocytes that P2Y(13) (purinergic receptor P2Y, G protein-coupled, 13) activation is essential for HDL uptake but the potential of P2Y(13) as a target to promote RCT has not been documented. Here, we show that P2Y(13)-deficient mice exhibited a decrease in hepatic HDL cholesterol uptake, hepatic cholesterol content, and biliary cholesterol output, although their plasma HDL and other lipid levels were normal. These changes translated into a substantial decrease in the rate of macrophage-to-feces RCT. Therefore, hallmark features of RCT are impaired in P2Y(13)-deficient mice. Furthermore, cangrelor, a partial agonist of P2Y(13), stimulated hepatic HDL uptake and biliary lipid secretions in normal mice and in mice with a targeted deletion of scavenger receptor class B type I (SR-BI) in liver (hypomSR-BI-knockout(liver)) but had no effect in P2Y(13) knockout mice, which indicate that P2Y(13)-mediated HDL uptake pathway is independent of SR-BI-mediated HDL selective cholesteryl ester uptake. CONCLUSION: These results establish P2Y(13) as an attractive novel target for modulating RCT and support the emerging view that steady-state plasma HDL levels do not necessarily reflect the capacity of HDL to promote RCT. |
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Authors:
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Aurélie C Fabre; Camille Malaval; Abduelhakem Ben Addi; Céline Verdier; Véronique Pons; Nizar Serhan; Laeticia Lichtenstein; Guillaume Combes; Thierry Huby; François Briand; Xavier Collet; Niels Nijstad; Uwe J F Tietge; Bernard Robaye; Bertrand Perret; Jean-Marie Boeynaems; Laurent O Martinez |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: 52 ISSN: 1527-3350 ISO Abbreviation: Hepatology Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-29 Completed Date: 2010-10-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: United States |
Other Details:
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Languages: eng Pagination: 1477-83 Citation Subset: IM |
Affiliation:
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Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 563, Toulouse, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Monophosphate
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analogs & derivatives,
pharmacology Animals Biological Transport Cholesterol / metabolism* Cholesterol, HDL / metabolism Lipoproteins, HDL / metabolism* Mice Mice, Knockout Receptors, Purinergic P2 / agonists, deficiency, physiology* Scavenger Receptors, Class B / deficiency |
| Chemical | |
Reg. No./Substance:
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0/Cholesterol, HDL; 0/Lipoproteins, HDL; 0/P2ry13 protein, mouse; 0/Receptors, Purinergic P2; 0/Scarb1 protein, mouse; 0/Scavenger Receptors, Class B; 0/cangrelor; 57-88-5/Cholesterol; 61-19-8/Adenosine Monophosphate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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