Cholesteryl ester flux from HDL to VLDL-1 is preferentially enhanced in type IIB hyperlipidemia in the postprandial state (original) (raw)

2002, The Journal of Lipid Research

Postprandial triglyceride-rich lipoproteins (TRL) exert proatherogenic effects at the arterial wall, including lipid deposition. Following consumption of a mixed meal (1,200 kcal), plasma-mediated cellular free cholesterol (FC) efflux, lecithin:cholesterol acyltransferase (LCAT), and cholesteryl ester transfer protein (CETP) activities were determined in subjects (n ‫؍‬ 12) displaying type IIB hyperlipidemia and compared with those in a normolipidemic control group (n ‫؍‬ 14). The relative capacity of plasma to induce FC efflux from Fu5AH cells via the SR-BI receptor was significantly increased 4 h postprandially ( ؉ 23%; P Ͻ 0.005) in the type IIB group, whereas it remained unchanged for postprandial plasma from normolipidemic subjects. LCAT activity was significantly elevated 2 h postprandially in both the IIB and control groups, ( ؉ 46% and ؉ 36%, respectively; P Ͻ 0.005 vs. respective baseline value). In type IIB subjects, total cholesteryl ester (CE) mass transfer from HDL to total TRL [chylomicrons (CMs) ؉ VLDL-1 ؉ VLDL-2 ؉ IDL] increased progressively from 15 ؎ 2 g CE/h/ml at baseline to 28 ؎ 2 g CE transferred/h/ml ( ؉ 87%; P ‫؍‬ 0.0004) at 4 h postprandially. CE transfer to CMs and VLDL-1 was preferentially stimulated (2.6-fold and 2.3-fold respectively) at 4 h in IIB subjects and occurred concomitantly with elevation in mass and particle number of both CMs (2.3-fold) and VLDL-1 (1.3-fold). Furthermore, in type IIB subjects, CETP-mediated total CE flux over the 8 h postprandial period from HDL to potentially atherogenic TRL was significantly enhanced, and notably to VLDL-1 (32-fold elevation; P Ͻ 0.005), relative to control subjects. Such CE transfer flux was reflected in a significant postprandial increase in CE-TG ratio in both CMs and VLDL-1 in type IIB plasmas. In conclusion, HDL-CE is preferentially targeted to VLDL-1 via the action of CETP during alimentary lipemia, thereby favoring formation and accumulation of atherogenic CE-rich remnant particles. ester flux from HDL to VLDL-1 is preferentially enhanced in type IIB hy-perlipidemia in the postprandial state. J. Lipid Res. 2002. 43: 1652-1660. Supplementary key words cholesteryl ester transfer protein • atherosclerosis • lecithin:cholesterol acyltransferase • cellular cholesterol efflux Abbreviations: CE, cholesteryl ester; CETP, cholesteryl ester transfer protein; TG, triglyceride; TRL, triglyceride-rich lipoprotein; CM, chylomicron; RCT, reverse cholesterol transport.