Abstract:
:MDCO-216, a complex of dimeric recombinant apoA-IMilano (apoA-IM) and palmitoyl-oleoyl-phosphatidylcholine (POPC), was administered to cynomolgus monkeys at 30, 100, and 300 mg/kg every other day for a total of 21 infusions, and effects on lipids, (apo)lipoproteins, and ex-vivo cholesterol efflux capacity were monitored. After 7 or 20 infusions, free cholesterol (FC) and phospholipids (PL) were strongly increased, and HDL-cholesterol (HDL-C), apoA-I, and apoA-II were strongly decreased. We then measured short-term effects on apoA-IM, lipids, and (apo)lipoproteins after the first or the last infusion. After the first infusion, PL and FC went up in the HDL region and also in the LDL and VLDL regions. ApoE shifted from HDL to LDL and VLDL regions, while ApoA-IM remained located in the HDL region. On day 41, ApoE levels were 8-fold higher than on day 1, and FC, PL, and apoE resided mostly in LDL and VLDL regions. Drug infusion quickly decreased the endogenous cholesterol esterification rate. ABCA1-mediated cholesterol efflux on day 41 was markedly increased, whereas scavenger receptor type B1 (SRB1) and ABCG1-mediated effluxes were only weakly increased. Strong increase of FC is due to sustained stimulation of ABCA1-mediated efflux, and drop in HDL and formation of large apoE-rich particles are due to lack of LCAT activation.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Kempen HJ,Gomaraschi M,Bellibas SE,Plassmann S,Zerler B,Collins HL,Adelman SJ,Calabresi L,Wijngaard PLdoi
10.1194/jlr.M033779subject
Has Abstractpub_date
2013-09-01 00:00:00pages
2341-53issue
9eissn
0022-2275issn
1539-7262pii
jlr.M033779journal_volume
54pub_type
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1971-01-01 00:00:00
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更新日期:1983-03-01 00:00:00
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journal_title:Journal of lipid research
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doi:
更新日期:1973-03-01 00:00:00
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pub_type: 杂志文章
doi:
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pub_type: 杂志文章
doi:
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doi:
更新日期:1988-03-01 00:00:00
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pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
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更新日期:1986-03-01 00:00:00
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更新日期:1985-07-01 00:00:00
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pub_type: 杂志文章
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更新日期:1978-09-01 00:00:00
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