HDL-apolipoprotein A-I exchange is independently associated with cholesterol efflux capacity |
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Authors: | Mark S Borja Kit F Ng Angela Irwin Jaekyoung Hong Xing Wu Daniel Isquith Xue-Qiao Zhao Bryan Prazen Virginia Gildengorin Michael N Oda Tomá? Vaisar |
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Institution: | *Children’s Hospital Oakland, Oakland, CA, 94609;†Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA, 98109;§Division of Cardiology, Harborview Medical Center, University of Washington, Seattle, WA, 98104;**Insilicos, Seattle, WA, 98109 |
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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. |
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Keywords: | high density lipoprotein high density lipoprotein/metabolism lipoproteins ATP binding cassette transporter A1 high density lipoprotein remodeling/exchange |
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