title: In vivo tissue cholesterol efflux is reduced in carriers of a mutation in APOA1.
abstract: Atheroprotection by high density lipoprotein (HDL) is considered to be mediated through reverse cholesterol transport (RCT) from peripheral tissues. We investigated in vivo cholesterol fluxes through the RCT pathway in patients with low plasma high density lipoprotein cholesterol (HDL-c) due to mutations in APOA1. Seven carriers of the L202P mutation in APOA1 (mean HDL-c: 20 ± 19 mg/dl) and seven unaffected controls (mean HDL-c: 54 ± 11 mg/dl, P < 0.0001) received a 20 h infusion of (13)C2-cholesterol ((13)C-C). Enrichment of plasma and erythrocyte free cholesterol and plasma cholesterol esters was measured. With a three-compartment SAAM-II model, tissue cholesterol efflux (TCE) was calculated. TCE was reduced by 19% in carriers (4.6 ± 0.8 mg/kg/h versus 5.7 ± 0.7 mg/kg/h in controls, P = 0.02). Fecal (13)C recovery and sterol excretion 7 days postinfusion did not differ significantly between carriers and controls: 21.3 ± 20% versus 13.3 ± 6.3% (P = 0.33), and 2,015 ± 1,431 mg/day versus 1456 ± 404 mg/day (P = 0.43), respectively. TCE is reduced in carriers of mutations in APOA1, suggesting that HDL contributes to efflux of tissue cholesterol in humans. The residual TCE and unaffected fecal sterol excretion in our severely affected carriers suggest, however, that non-HDL pathways contribute to RCT significantly.
authors: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Adriaan G
authors: AG
authors: Holleboom
authors: Lily
authors: L
authors: Jakulj
authors: Remco
authors: R
authors: Franssen
authors: Julie
authors: J
authors: Decaris
authors: Menno
authors: M
authors: Vergeer
authors: Joris
authors: J
authors: Koetsveld
authors: Jayraz
authors: J
authors: Luchoomun
authors: Alexander
authors: A
authors: Glass
authors: Marc K
authors: MK
authors: Hellerstein
authors: John J P
authors: JJ
authors: Kastelein
authors: G Kees
authors: GK
authors: Hovingh
authors: Jan Albert
authors: JA
authors: Kuivenhoven
authors: Albert K
authors: AK
authors: Groen
authors: Scott M
authors: SM
authors: Turner
authors: Erik S G
authors: ES
authors: Stroes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055815:Young Adult
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL
keywords: fecal sterol excretion; genetics; high density lipoprotein; reverse cholesterol transport
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