1. HDL-apolipoprotein A-I exchange is independently associated with cholesterol efflux capacity
- Author
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Mark S. Borja, Kit F. Ng, Angela Irwin, Jaekyoung Hong, Xing Wu, Daniel Isquith, Xue-Qiao Zhao, Bryan Prazen, Virginia Gildengorin, Michael N. Oda, and Tomáš Vaisar
- Subjects
high density lipoprotein ,high density lipoprotein/metabolism ,lipoproteins ,ATP binding cassette transporter A1 ,high density lipoprotein remodeling/exchange ,Biochemistry ,QD415-436 - 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.
- Published
- 2015
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