Newly developed apolipoprotein A-I mimetic peptide promotes macrophage reverse cholesterol transport in vivo

Background: We elucidated the effect of newly developed Fukuoka Apolipoprotein A-I Mimetic Peptide (FAMP) on in vivo macrophage reverse cholesterol transport (RCT) and the underlying mechanisms. Methods and results: Cholesteryl ester transfer protein transgenic mice were divided into FAMP, and placebo control groups, and injected with FAMP or phosphate buffer saline intraperitoneally for 5 days. The FAMP group showed a significant decrease in plasma high-density lipoprotein cholesterol (HDL-C), and plasma from the FAMP group had an increased ability to promote ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux from bone marrow macrophages ex vivo. Furthermore, mice were injected intraperitoneally with H-3-cholesterol-labeled and cholesterol-loaded macrophages and monitored for the appearance of H-3-tracer. The amount of 3H-tracer excreted into feces over 48 h in the FAMP group was significantly higher than that in the control group. H-3-cholesterol ester (CE)-HDL was injected intravenously and 3H-cholesterol in blood was counted. In the FAMP group, plasma H-3-CE-HDL decreased rapidly, and treatment with FAMP markedly increased the fractional catabolic rate. Conclusions: The administration of FAMP promoted ABCA1-dependent efflux ex vivo, HDL turnover in vivo, and macrophage RCT in vivo despite reduced plasma HDL-C levels. FAMP might have atheroprotective potential. (C) 2015 Elsevier Ireland Ltd. All rights reserved.