Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo

• 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
• Subjects: apolipoprotein A-I; kinetics; lipoproteins; nonhuman primates; ABCA1; SRB1
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520308427

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.