Apolipoprotein A5 ‐ enriched HDL is Poor Acceptor for Cholesterol in in vitro Efflux Study

Abstract

High density lipoprotein (HDL) plays central role in reverse cholesterol (CH) transport (RCT). Although apolipoprotein A5, a modulator of triglyceride‐rich lipoprotein metabolism, is abundant on HDL its effect on HDL‐driven RCT has not been elucidated. To test this macrophages loaded with 3H‐ CH were incubated with whole plasma, total HDL (d=1.063–1.21), HDL3 (d=1.063–1.09), preβ‐HDL (d=1.15–1.21) from apoA5 transgenic (A5tg) and from background mice. Lipoproteins from A5tg mice were associated with significantly (p<0.05) lower CH efflux (expressed as % of medium/medium + cells cpm): 54.0 ± 4.0 vs. 35 ± 2.0 in the presence of whole plasma, 19.9 ± 4.0 vs. 12.2 ± 2.0 in the presence of total HDL, 28 ± 5.0 vs. 16.0 ± 3.0 in the presence of HDL3, 8.2 ± 2.0 vs. 4.2 ± 1.0 in the presence of preβ‐HDL. When we use HDL2 (d=1.09–1.15) as acceptor, CH efflux for A5tg mice was comparable to background FVB mice. Additionally, no difference in CH efflux between the two mice strains was demonstrated in experiments that used as acceptor very low density lipoprotein (VLDL) ‐ a lipoprotein that does not involve lecithin‐cholesterol acyltransferase (LCAT) activity. While potential underlying case include differences between the groups in both lipid and apoprotein content of HDL, the lack of difference between the groups in the VLDL experiments supports the possibility that interference of apoA5 with the activity of LCAT is a likely mechanism.