Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo

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Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo

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Title: Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo
Author: Sacks, Frank Martin; Rudel, L. L.; Conner, A.; Akeefe, H.; Kostner, G.; Baki, T.; Rothblat, G.; de la Llera-Moya, M.; Asztalos, B.; Perlman, T.; Zheng, Chunyu; Alaupovic, P.; Maltais, J.-A. B.; Brewer, H. B.

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Citation: Sacks, F. M., L. L. Rudel, A. Conner, H. Akeefe, G. Kostner, T. Baki, G. Rothblat, et al. 2008. “Selective Delipidation of Plasma HDL Enhances Reverse Cholesterol Transport in Vivo.” The Journal of Lipid Research 50 (5) (December 19): 894–907. doi:10.1194/jlr.m800622-jlr200.
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Abstract: 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 alpha, prebeta-1, and other prebeta 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. Prebeta-1-like HDL had a plasma residence time of 8 +/- 6 h and was converted entirely to large alpha-HDL having residence times of 13-14 h. Small alpha-HDL was converted entirely to large alpha-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.
Published Version: doi:10.1194/jlr.M800622-JLR200
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