Document Detail


Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells.
MedLine Citation:
PMID:  22855736     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
HDL particles may enter atherosclerotic lesions having an acidic intimal fluid. Therefore, we investigated whether acidic pH would affect their structural and functional properties. For this purpose, HDL(2) and HDL(3) subfractions were incubated for various periods of time at different pH values ranging from 5.5 to 7.5, after which their protein and lipid compositions, size, structure, and cholesterol efflux capacity were analyzed. Incubation of either subfraction at acidic pH induced unfolding of apolipoproteins, which was followed by release of lipid-poor apoA-I and ensuing fusion of the HDL particles. The acidic pH-modified HDL particles exhibited an enhanced ability to promote cholesterol efflux from cholesterol-laden primary human macrophages. Importantly, treatment of the acidic pH-modified HDL with the mast cell-derived protease chymase completely depleted the newly generated lipid-poor apoA-I, and prevented the acidic pH-dependent increase in cholesterol efflux. The above-found pH-dependent structural and functional changes were stronger in HDL(3) than in HDL(2). Spontaneous acidic pH-induced remodeling of mature spherical HDL particles increases HDL-induced cholesterol efflux from macrophage foam cells, and therefore may have atheroprotective effects.
Authors:
Su Duy Nguyen; Katariina Öörni; Miriam Lee-Rueckert; Tero Pihlajamaa; Jari Metso; Matti Jauhiainen; Petri T Kovanen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-01
Journal Detail:
Title:  Journal of lipid research     Volume:  53     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-07     Completed Date:  2013-01-29     Revised Date:  2013-10-10    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2115-25     Citation Subset:  IM    
Affiliation:
Wihuri Research Institute, Kalliolinnantie 4, FIN-00140, Helsinki, Finland.
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MeSH Terms
Descriptor/Qualifier:
Apolipoprotein A-I / metabolism
Cholesterol / metabolism*
Chymases / metabolism
Foam Cells / metabolism*
Humans
Hydrogen-Ion Concentration
Lipoproteins, HDL / metabolism*
Macrophages / metabolism*
Chemical
Reg. No./Substance:
0/Apolipoprotein A-I; 0/Lipoproteins, HDL; 57-88-5/Cholesterol; EC 3.4.21.39/Chymases
Comments/Corrections

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