Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 29, Issue 10, Pages 1496-U202Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.109.191379
Keywords
apoA-I Milano; reverse cholesterol transport; high-density lipoprotein; macrophage; apolipoprotein
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Funding
- AHA [0625372U]
- NIH [HL22633, HL063768, HL59407]
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Objective-To compare the abilities of human wild-type apoA-I (WT apoA-I) and human apoA-I-Milano (apoA-I-M) to promote macrophage reverse cholesterol transport (RCT) in apoA-I-null mice infected with adeno-associated virus (AAV) expressing either WT apoA-I or apoA-I-M. Methods and Results-WT apoA-I- or apoA-I-M-expressing mice were intraperitoneally injected with [H-3]cholesterol-labeled J774 mouse macrophages. After 48 hours, no significant difference was detected in the amount of cholesterol removed from the macrophages and deposited in the feces via the RCT pathway between the WT apoA-I and apoA-I-M groups. Analysis of the individual components of the RCT pathway demonstrated that the apoA-I-M-expressing mice promoted ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux as efficiently as WT apoA-I but that apoA-I-M had a reduced ability to promote cholesterol esterification via lecithin cholesterol-acyltransferase (LCAT). This resulted in reduced cholesteryl ester (CE) and increased free cholesterol (FC) levels in the plasma of mice expressing apoA-I-M compared to WT apoA-I. These differences did not affect the rate of delivery of labeled cholesterol to the liver via SR-BI-mediated selective uptake or its subsequent excretion in the feces. Conclusion-Within the limits of the in vivo assay, WT apoA-I and apoA-I-M are equally efficient at promoting macrophage RCT, suggesting that if apoA- I-M is more atheroprotective than WT apoA-I it is not attributable to an enhancement of macrophage RCT. (Arterioscler Thromb Vasc Biol. 2009; 29: 1496-1501.)
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