title: Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo.
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.
authors.affiliation: Harvard School of Public Health and Harvard Medical School, Boston, MA, USA, USA. fsacks@hsph.harvard.edu
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sacks
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Rudel
authors.forename: Adam
authors.initials: A
authors.lastname: Conner
authors.forename: Hassibullah
authors.initials: H
authors.lastname: Akeefe
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kostner
authors.forename: Talal
authors.initials: T
authors.lastname: Baki
authors.forename: George
authors.initials: G
authors.lastname: Rothblat
authors.forename: Margarita
authors.initials: M
authors.lastname: de la Llera-Moya
authors.forename: Bela
authors.initials: B
authors.lastname: Asztalos
authors.forename: Timothy
authors.initials: T
authors.lastname: Perlman
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zheng
authors.forename: Petar
authors.initials: P
authors.lastname: Alaupovic
authors.forename: Jo-Ann B
authors.initials: JA
authors.lastname: Maltais
authors.forename: H Bryan
authors.initials: HB
authors.lastname: Brewer
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000473:pathology; D016632:Apolipoprotein A-I / Q000378:metabolism; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology; D001692:Biological Transport; D002460:Cell Line; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry; D051379:Mice; D051122:Scavenger Receptors, Class B / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D002784:Cholesterol