title: HDL-apolipoprotein A-I exchange is independently associated with cholesterol efflux capacity.
abstract: HDL is the primary mediator of cholesterol mobilization from the periphery to the liver via reverse cholesterol transport (RCT). A critical first step in this process is the uptake of cholesterol from lipid-loaded macrophages by HDL, a function of HDL inversely associated with prevalent and incident cardiovascular disease. We hypothesized that the dynamic ability of HDL to undergo remodeling and exchange of apoA-I is an important and potentially rate-limiting aspect of RCT. In this study, we investigated the relationship between HDL-apoA-I exchange (HAE) and serum HDL cholesterol (HDL-C) efflux capacity. We compared HAE to the total and ABCA1-specific cholesterol efflux capacity of 77 subjects. We found that HAE was highly correlated with both total (r = 0.69, P < 0.0001) and ABCA1-specific (r = 0.47, P < 0.0001) efflux, and this relationship remained significant after adjustment for HDL-C or apoA-I. Multivariate models of sterol efflux capacity indicated that HAE accounted for approximately 25% of the model variance for both total and ABCA1-specific efflux. We conclude that the ability of HDL to exchange apoA-I and remodel, as measured by HAE, is a significant contributor to serum HDL efflux capacity, independent of HDL-C and apoA-I, indicating that HDL dynamics are an important factor in cholesterol efflux capacity and likely RCT.
authors.affiliation: Children's Hospital Oakland, Oakland, CA 94609.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Borja
authors.affiliation: Children's Hospital Oakland, Oakland, CA 94609.
authors.forename: Kit F
authors.initials: KF
authors.lastname: Ng
authors.affiliation: Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA 98109.
authors.forename: Angela
authors.initials: A
authors.lastname: Irwin
authors.affiliation: Division of Cardiology, Harborview Medical Center, University of Washington, Seattle, WA 98104.
authors.forename: Jaekyoung
authors.initials: J
authors.lastname: Hong
authors.affiliation: Division of Cardiology, Harborview Medical Center, University of Washington, Seattle, WA 98104.
authors.forename: Xing
authors.initials: X
authors.lastname: Wu
authors.affiliation: Division of Cardiology, Harborview Medical Center, University of Washington, Seattle, WA 98104.
authors.forename: Daniel
authors.initials: D
authors.lastname: Isquith
authors.affiliation: Division of Cardiology, Harborview Medical Center, University of Washington, Seattle, WA 98104.
authors.forename: Xue-Qiao
authors.initials: XQ
authors.lastname: Zhao
authors.affiliation: Insilicos, Seattle, WA 98109.
authors.forename: Bryan
authors.initials: B
authors.lastname: Prazen
authors.affiliation: Children's Hospital Oakland, Oakland, CA 94609.
authors.forename: Virginia
authors.initials: V
authors.lastname: Gildengorin
authors.affiliation: Children's Hospital Oakland, Oakland, CA 94609.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Oda
authors.affiliation: Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA 98109.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Vaisar
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000097:blood*; D000369:Aged, 80 and over; D016632:Apolipoprotein A-I / Q000097:blood*; D001692:Biological Transport; D002318:Cardiovascular Diseases / Q000097:blood; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL
keywords: ATP binding cassette transporter A1; high density lipoprotein; high density lipoprotein remodeling/exchange; high density lipoprotein/metabolism; lipoproteins