Cholesteryl ester flux from HDL to VLDL-1 is preferentially enhanced in type IIB hyperlipidemia in the postprandial state.

Abstract

Postprandial triglyceride-rich lipoproteins (TRL) exert proatherogenic effects at the arterial wall, including lipid deposition. Following consumption of a mixed meal (1200 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 < 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 < 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 micro g CE/h/ml at baseline to 28 +/- 2 micro 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 < 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.

• Authors: Maryse Guerin, Pascal Egger, Céline Soudant, Wilfried Le Goff, Arie van Tol, Reynald Dupuis, M John Chapman
• Journal: Journal of lipid research (J Lipid Res) Vol. 43 Issue 10 Pg. 1652-60 (Oct 2002) ISSN: 0022-2275 [Print] United States
• PMID: 12364549 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CETP protein, human
• Carrier Proteins
• Cholesterol Ester Transfer Proteins
• Cholesterol Esters
• Cholesterol, HDL
• Cholesterol, VLDL
• Glycoproteins
• Lipoproteins
• Triglycerides
• Phosphatidylcholine-Sterol O-Acyltransferase

Topics

• Adult
• Aged
• Analysis of Variance
• Carrier Proteins (pharmacology)
• Cholesterol Ester Transfer Proteins
• Cholesterol Esters (blood)
• Cholesterol, HDL (blood)
• Cholesterol, VLDL (blood)
• Glycoproteins
• Humans
• Hyperlipoproteinemia Type II (blood)
• Kinetics
• Lipoproteins (blood)
• Male
• Middle Aged
• Phosphatidylcholine-Sterol O-Acyltransferase (blood)
• Postprandial Period
• Triglycerides (blood)