Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo

Uptake of cholesterol from peripheral cells by nascent small HDL circulating in plasma is necessary to prevent atherosclerosis. This process, termed reverse cholesterol transport, produces larger cholesterol-rich HDL that transfers its cholesterol to the liver facilitating excretion. Most HDL in pla...

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Bibliographic Details
Main Authors: Frank M. Sacks, Lawrence L. Rudel, Adam Conner, Hassibullah Akeefe, Gerhard Kostner, Talal Baki, George Rothblat, Margarita de la Llera-Moya, Bela Asztalos, Timothy Perlman, Chunyu Zheng, Petar Alaupovic, Jo-Ann B. Maltais, H. Bryan Brewer
Format: Article
Language:English
Published: Elsevier 2009-05-01
Series:Journal of Lipid Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520308427
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Summary:Uptake of cholesterol from peripheral cells by nascent small HDL circulating in plasma is necessary to prevent atherosclerosis. This process, termed reverse cholesterol transport, produces larger cholesterol-rich HDL that transfers its cholesterol to the liver facilitating excretion. Most HDL in plasma is cholesterol-rich. We demonstrate that treating plasma with a novel selective delipidation procedure converts large to small HDL [HDL-selectively delipidated (HDL-sdl)]. HDL-sdl contains several cholesterol-depleted species resembling small α, preβ-1, and other preβ forms. Selective delipidation markedly increases efficacy of plasma to stimulate ABCA1-mediated cholesterol transfer from monocytic cells to HDL. Plasma from African Green monkeys underwent selective HDL delipidation. The delipidated plasma was reinfused into five monkeys. Preβ-1-like HDL had a plasma residence time of 8 ± 6 h and was converted entirely to large α-HDL having residence times of 13–14 h. Small α-HDL was converted entirely to large α-HDL. These findings suggest that selective HDL delipidation activates reverse cholesterol transport, in vivo and in vitro. Treatment with delipidated plasma tended to reduce diet-induced aortic atherosclerosis in monkeys measured by intravascular ultrasound. These findings link the conversion of small to large HDL, in vivo, to improvement in atherosclerosis.
ISSN:0022-2275