Niemann-Pick C1 protects against atherosclerosis in mice via regulation of macrophage intracellular cholesterol trafficking
J. Clin. Invest. Jessie R. Zhang, et al. 118:2281 doi:10.1172/JCI32561 [
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Figure 5Reduced expression of cholesterol transporters and cholesterol efflux in Mϕ
Npc1–/– chimeric mice.
(
A)
Abca1 and
Abcg1 gene expression in peritoneal macrophages harvested from high-fat diet–fed Mϕ
Npc1+/+ and Mϕ
Npc1–/– mice. Expression was determined by real-time quantitative RT-PCR and normalized to expression in Mϕ
Npc1+/+ macrophages. (
B and
C) Cholesterol efflux to apoA-I and HDL from peritoneal macrophages harvested from high-fat diet–fed Mϕ
Npc1+/+ and Mϕ
Npc1–/– mice. Cells were incubated overnight with AcLDL labeled with [
3H]cholesterol, followed by incubation for 4 (
B) or 24 hours (
C) in medium containing 0.2% BSA with 10 μg/ml human apoA-I or 50 μg/ml human HDL. ApoA-I– or HDL-specific cholesterol efflux is shown as the radioactivity released from the cells into the medium, expressed as a percentage relative to the total radioactivity in cells and media. T/9-cis RA, T0901317. Data are mean ± SEM of triplicate determinations and are representative of 2 independent experiments. *
P ≤ 0.05, **
P ≤ 0.01 versus respective Mϕ
Npc1+/+;
#P ≤ 0.05,
##P ≤ 0.01 versus respective untreated Mϕ
Npc1–/–;
†P = NS versus untreated ApoA-I Mϕ
Npc1+/+.