Intravenous apoA-I/lecithin discs increase pre-β-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humans

The extent to which plasma HDL concentration regulates reverse cholesterol transport (RCT) is not known. The principal acceptors of unesterified cholesterol (UC) from cultured cells are small pre-β-HDL, which we have shown increase in plasma during intravenous infusion of apolipoprotein A-I/phosphat...

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Main Authors: M.N. Nanjee, C.J. Cooke, R. Garvin, F. Semeria, G. Lewis, W.L. Olszewski, N.E. Miller
Format: Article
Language:English
Published: Elsevier 2001-10-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520322124
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author M.N. Nanjee
C.J. Cooke
R. Garvin
F. Semeria
G. Lewis
W.L. Olszewski
N.E. Miller
author_facet M.N. Nanjee
C.J. Cooke
R. Garvin
F. Semeria
G. Lewis
W.L. Olszewski
N.E. Miller
author_sort M.N. Nanjee
collection DOAJ
description The extent to which plasma HDL concentration regulates reverse cholesterol transport (RCT) is not known. The principal acceptors of unesterified cholesterol (UC) from cultured cells are small pre-β-HDL, which we have shown increase in plasma during intravenous infusion of apolipoprotein A-I/phosphatidylcholine (apoA-I/PC) discs in humans. We have now examined the effects on tissue fluid HDL and RCT. ApoA-I/PC or proapoA-I/PC discs were infused into 16 healthy males. Eleven had been given intravenous radiocholesterol to label tissue pools; in 12 prenodal leg lymph was collected throughout; and in 8 all feces were collected. The rise in small pre-β-HDL in plasma was associated with increases in 1) pre-β-HDL concentration in lymph (all subjects), 2) the size of other lymph HDL (four of four subjects), 3) the cholesterol content of lymph lipoproteins relative to plasma lipoproteins (P < 0.01, n = 4), 4) cholesterol-specific radioactivity in lymph (five of nine subjects), 5) plasma lathosterol (P < 0.004, n = 4), 6) plasma cholesterol esterification rate (P < 0.001, n = 4), and 7) fecal bile acid excretion (P < 0.001, n = 8).These results support the hypothesis that small pre-β-HDL generated in plasma readily cross endothelium into tissue fluid, and thereby promote efflux of UC from peripheral cells. After delivery to the liver, peripheral cholesterol appears to be utilized more for bile acid synthesis than for biliary cholesterol secretion in humans.
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spelling doaj.art-1c30cf42c73043de8f2f069980710b3b2022-12-21T22:30:40ZengElsevierJournal of Lipid Research0022-22752001-10-01421015861593Intravenous apoA-I/lecithin discs increase pre-β-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humansM.N. Nanjee0C.J. Cooke1R. Garvin2F. Semeria3G. Lewis4W.L. Olszewski5N.E. Miller6Department of Cardiovascular Biochemistry, St. Bartholomew's and Royal London School of Medicine and Dentistry, Charterhouse Square, London ECIM 6BQ, UKDepartment of Cardiovascular Biochemistry, St. Bartholomew's and Royal London School of Medicine and Dentistry, Charterhouse Square, London ECIM 6BQ, UKDepartment of Cardiovascular Biochemistry, St. Bartholomew's and Royal London School of Medicine and Dentistry, Charterhouse Square, London ECIM 6BQ, UKDepartment of Cardiovascular Biochemistry, St. Bartholomew's and Royal London School of Medicine and Dentistry, Charterhouse Square, London ECIM 6BQ, UKDepartment of Cardiovascular Biochemistry, St. Bartholomew's and Royal London School of Medicine and Dentistry, Charterhouse Square, London ECIM 6BQ, UKDepartment of Cardiovascular Biochemistry, St. Bartholomew's and Royal London School of Medicine and Dentistry, Charterhouse Square, London ECIM 6BQ, UK; Department of Surgical Research and Transplantology, Medical Research Center, Polish Academy of Sciences, Warsaw, PolandDepartment of Cardiovascular Biochemistry, St. Bartholomew's and Royal London School of Medicine and Dentistry, Charterhouse Square, London ECIM 6BQ, UK; To whom correspondence should be addressed. e-mail:The extent to which plasma HDL concentration regulates reverse cholesterol transport (RCT) is not known. The principal acceptors of unesterified cholesterol (UC) from cultured cells are small pre-β-HDL, which we have shown increase in plasma during intravenous infusion of apolipoprotein A-I/phosphatidylcholine (apoA-I/PC) discs in humans. We have now examined the effects on tissue fluid HDL and RCT. ApoA-I/PC or proapoA-I/PC discs were infused into 16 healthy males. Eleven had been given intravenous radiocholesterol to label tissue pools; in 12 prenodal leg lymph was collected throughout; and in 8 all feces were collected. The rise in small pre-β-HDL in plasma was associated with increases in 1) pre-β-HDL concentration in lymph (all subjects), 2) the size of other lymph HDL (four of four subjects), 3) the cholesterol content of lymph lipoproteins relative to plasma lipoproteins (P < 0.01, n = 4), 4) cholesterol-specific radioactivity in lymph (five of nine subjects), 5) plasma lathosterol (P < 0.004, n = 4), 6) plasma cholesterol esterification rate (P < 0.001, n = 4), and 7) fecal bile acid excretion (P < 0.001, n = 8).These results support the hypothesis that small pre-β-HDL generated in plasma readily cross endothelium into tissue fluid, and thereby promote efflux of UC from peripheral cells. After delivery to the liver, peripheral cholesterol appears to be utilized more for bile acid synthesis than for biliary cholesterol secretion in humans.http://www.sciencedirect.com/science/article/pii/S0022227520322124proapolipoprotein A-Iphospholipidsnascent HDLlymphcholesterol esterificationstigmastanol
spellingShingle M.N. Nanjee
C.J. Cooke
R. Garvin
F. Semeria
G. Lewis
W.L. Olszewski
N.E. Miller
Intravenous apoA-I/lecithin discs increase pre-β-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humans
Journal of Lipid Research
proapolipoprotein A-I
phospholipids
nascent HDL
lymph
cholesterol esterification
stigmastanol
title Intravenous apoA-I/lecithin discs increase pre-β-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humans
title_full Intravenous apoA-I/lecithin discs increase pre-β-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humans
title_fullStr Intravenous apoA-I/lecithin discs increase pre-β-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humans
title_full_unstemmed Intravenous apoA-I/lecithin discs increase pre-β-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humans
title_short Intravenous apoA-I/lecithin discs increase pre-β-HDL concentration in tissue fluid and stimulate reverse cholesterol transport in humans
title_sort intravenous apoa i lecithin discs increase pre β hdl concentration in tissue fluid and stimulate reverse cholesterol transport in humans
topic proapolipoprotein A-I
phospholipids
nascent HDL
lymph
cholesterol esterification
stigmastanol
url http://www.sciencedirect.com/science/article/pii/S0022227520322124
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