title: Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells.
abstract: 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.affiliation: Wihuri Research Institute, Kalliolinnantie 4, FIN-00140, Helsinki, Finland.
authors.forename: Su Duy
authors.initials: SD
authors.lastname: Nguyen
authors.affiliation: Wihuri Research Institute, Kalliolinnantie 4, FIN-00140, Helsinki, Finland.
authors.forename: Katariina
authors.initials: K
authors.lastname: Öörni
authors.affiliation: Wihuri Research Institute, Kalliolinnantie 4, FIN-00140, Helsinki, Finland.
authors.forename: Miriam
authors.initials: M
authors.lastname: Lee-Rueckert
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Tero
authors.initials: T
authors.lastname: Pihlajamaa
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Metso
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.affiliation: Wihuri Research Institute, Kalliolinnantie 4, FIN-00140, Helsinki, Finland. Electronic address: petri.kovanen@wri.fi.
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
mesh_terms: D016632:Apolipoprotein A-I / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D053818:Chymases / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D002784:Cholesterol; D053818:Chymases