HDL-apolipoprotein A-I exchange is independently associated with cholesterol efflux capacity.
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.
['Borja|Mark S|MS|', 'Ng|Kit F|KF|', 'Irwin|Angela|A|', 'Hong|Jaekyoung|J|', 'Wu|Xing|X|', 'Isquith|Daniel|D|', 'Zhao|Xue-Qiao|XQ|', 'Prazen|Bryan|B|', 'Gildengorin|Virginia|V|', 'Oda|Michael N|MN|', 'Vaisar|Tomáš|T|']
D064286:ATP Binding Cassette Transporter 1 D000369:Aged, 80 and over D016632:Apolipoprotein A-I D001692:Biological Transport D002318:Cardiovascular Diseases D002478:Cells, Cultured D008076:Cholesterol, HDL D005260:Female D006801:Humans D008264:Macrophages D008297:Male
ATP binding cassette transporter A1 high density lipoprotein high density lipoprotein remodeling/exchange high density lipoprotein/metabolism lipoproteins