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

BackgroundWe 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 resultsCholesteryl 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 3H-cholesterol-labeled and cholesterol-loaded macrophages and monitored for the appearance of 3H-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. 3H-cholesterol ester (CE)-HDL was injected intravenously and 3H-cholesterol in blood was counted. In the FAMP group, plasma 3H-CE-HDL decreased rapidly, and treatment with FAMP markedly increased the fractional catabolic rate.ConclusionsThe 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.