| Acidic extracellular environments strongly impair ABCA1-mediated cholesterol efflux from human macrophage foam cells. | |
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MedLine Citation:
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PMID: 20702810 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: In the deep microenvironments of advanced human atherosclerotic lesions, the intimal fluid becomes acidic. We examined the effect of an acidic extracellular pH on cholesterol removal (efflux) from primary human macrophages. METHODS AND RESULTS: When cholesterol efflux from acetyl-low-density lipoprotein-loaded macrophages to various cholesterol acceptors was evaluated at pH 7.5, 6.5, or 5.5, the lower the pH the more was cholesterol efflux reduced. The reduction of efflux to lipid-free apolipoprotein A-I was stronger than to high-density lipoprotein(2) or to plasma. Cholesterol efflux to every acceptor was severely compromised also at neutral pH when the macrophages had been loaded with cholesterol at acidic pH, or when both loading and efflux were carried out at acidic pH. Compatible with these observations, the typical upregulation of ABCA1 and ABCG1 mRNA levels in macrophages loaded with cholesterol at neutral pH was rapidly attenuated in acidic medium. The secondary structure of apolipoprotein A-I did not changed over the pH range studied, supporting the notion that the inhibitory effect of acidic pH on cholesterol efflux rather impaired the ability of the foam cells to facilitate ABCA1-mediated cholesterol release. Secretion of apolipoprotein E from the foam cells was fully inhibited when the pH was 5.5, which further reduced cholesterol efflux. CONCLUSIONS: An acidic pH reduces cholesterol efflux via different pathways and particularly impairs the function of the ABCA1 transporter. The pH-sensitive function of human macrophage foam cells in releasing cholesterol may accelerate lipid accumulation in deep areas of advanced atherosclerotic plaques where the intimal fluid is acidic. |
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Authors:
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Miriam Lee-Rueckert; Jani Lappalainen; Hannele Leinonen; Tero Pihlajamaa; Matti Jauhiainen; Petri T Kovanen |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-11 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 30 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-19 Completed Date: 2010-09-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1766-72 Citation Subset: IM |
Affiliation:
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Wihuri Research Institute, Helsinki 00140, Finland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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genetics,
metabolism* Apolipoprotein A-I / chemistry, metabolism Biological Transport Cells, Cultured Cholesterol / metabolism* Down-Regulation Foam Cells / metabolism* Humans Hydrogen-Ion Concentration Kinetics Lipoproteins, HDL2 / metabolism Lipoproteins, LDL / metabolism Protein Structure, Secondary RNA, Messenger / metabolism |
| Chemical | |
Reg. No./Substance:
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0/ABCG1 protein, human; 0/APOA1 protein, human; 0/ATP binding cassette transporter 1; 0/ATP-Binding Cassette Transporters; 0/Apolipoprotein A-I; 0/Lipoproteins, HDL2; 0/Lipoproteins, LDL; 0/RNA, Messenger; 0/acetyl-LDL; 57-88-5/Cholesterol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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