Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells
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, HDL2 and HDL3 subfractions were incubated for various periods of time at different pH values ranging...
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| Format: | Article |
| Language: | English |
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Elsevier
2012-10-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520431888 |
| _version_ | 1818662363048443904 |
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| author | Su Duy Nguyen Katariina Öörni Miriam Lee-Rueckert Tero Pihlajamaa Jari Metso Matti Jauhiainen Petri T. Kovanen |
| author_facet | Su Duy Nguyen Katariina Öörni Miriam Lee-Rueckert Tero Pihlajamaa Jari Metso Matti Jauhiainen Petri T. Kovanen |
| author_sort | Su Duy Nguyen |
| collection | DOAJ |
| description | 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, HDL2 and HDL3 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 HDL3 than in HDL2. 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. |
| first_indexed | 2024-12-17T04:59:45Z |
| format | Article |
| id | doaj.art-42dedde61301410cb3b83c1f050bba55 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T04:59:45Z |
| publishDate | 2012-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-42dedde61301410cb3b83c1f050bba552022-12-21T22:02:35ZengElsevierJournal of Lipid Research0022-22752012-10-01531021152125Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cellsSu Duy Nguyen0Katariina Öörni1Miriam Lee-Rueckert2Tero Pihlajamaa3Jari Metso4Matti Jauhiainen5Petri T. Kovanen6Wihuri Research Institute, Kalliolinnantie 4, FIN-00140, Helsinki, FinlandWihuri Research Institute, Kalliolinnantie 4, FIN-00140, Helsinki, FinlandWihuri Research Institute, Kalliolinnantie 4, FIN-00140, Helsinki, FinlandInstitute of Biotechnology, University of Helsinki, Helsinki, FinlandNational Institute for Health and Welfare, Helsinki, FinlandNational Institute for Health and Welfare, Helsinki, FinlandTo whom correspondence should be addressed; Wihuri Research Institute, Kalliolinnantie 4, FIN-00140, Helsinki, FinlandHDL 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, HDL2 and HDL3 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 HDL3 than in HDL2. 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.http://www.sciencedirect.com/science/article/pii/S0022227520431888fusionatherosclerosischymasehigh density lipoprotein |
| spellingShingle | Su Duy Nguyen Katariina Öörni Miriam Lee-Rueckert Tero Pihlajamaa Jari Metso Matti Jauhiainen Petri T. Kovanen Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells Journal of Lipid Research fusion atherosclerosis chymase high density lipoprotein |
| title | Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells |
| title_full | Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells |
| title_fullStr | Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells |
| title_full_unstemmed | Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells |
| title_short | Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells |
| title_sort | spontaneous remodeling of hdl particles at acidic ph enhances their capacity to induce cholesterol efflux from human macrophage foam cells |
| topic | fusion atherosclerosis chymase high density lipoprotein |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520431888 |
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