Potencies of Lipoproteins in Fasting and Postprandial Plasma to Accept Additional Cholesterol Molecules Released From Cell Membranes

Chung, Byung Hong; Franklin, Frank A.; Cho, B. H. Simon; Segrest, Jere P.; Hart, Karen; Darnell, Betty E.

doi:10.1161/01.atv.18.8.1217

Cited by 21 publications

(22 citation statements)

References 52 publications

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“…Postprandial lipemia observed in type IIB subjects was significantly associated with increase (ϩ23%; P Ͻ 0.005) at 2 h in the capacity of whole plasma to efflux cellular free cholesterol. This finding is consistent with a previous report (18) in which postprandial as compared with fasting plasma was more potent in promoting free cholesterol efflux from red blood cells; the mechanism of such efflux remains indeterminate however, but may primarily involve efflux of cholesterol by receptor-independent, passive diffusion. Earlier studies (13,34) have demonstrated that pre␤-HDL constitute preferential acceptors of cellular free cholesterol and thus increased levels of pre␤ HDL particles in plasma may enhance cholesterol efflux.…”

Section: Discussionsupporting

confidence: 93%

“…Such particles are a substrate for LCAT, and thus postprandial lipemia is characterized by activation of plasma LCAT activity (14)(15)(16)(17), a finding which led to the proposal that the postprandial phase is associated with activation of RCT (14). In earlier studies, the capacity of postprandial plasma lipoproteins from healthy normolipidemic subjects to promote receptor-independent cholesterol efflux from cell membranes was evaluated (18). Using red blood cells as donors of membrane cholesterol via passive diffusion in the aqueous phase, CMs were shown to represent the most potent acceptors of free cholesterol among postprandial lipoproteins.…”

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confidence: 99%

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

Guérin

Egger

Soudant

et al. 2002

Journal of Lipid Research

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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. In order to maintain cholesterol homeostasis in peripheral tissues, excess cellular cholesterol is returned to the liver for excretion via a multistep process termed "reverse cholesterol transport" (RCT) (1). A key component of this process involves the transfer of a significant portion of the cholesteryl ester (CE) pool in HDL to apoB-containing lipoproteins (VLDL, IDL, and LDL) via the action of the cholesteryl ester transfer protein (CETP) (2).Hyperlipidemia of phenotype IIB is associated with an increased risk of premature coronary artery disease and is characterized by concomitant elevation of circulating levels of atherogenic apoB-containing, triglyceride-rich (VLDL) and cholesterol-rich lipoproteins (VLDL remnants, IDL, and LDL including small, dense LDL) (3). In type IIB hyperlipidemia during the fasting state, CETP is implicated in the intravascular formation of atherogenic small, dense LDL through an indirect mechanism involving an elevated rate of CE transfer from HDL to VLDL, and more specifically, to large VLDL-1 particles (4, 5)....

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

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

Guérin

Egger

Soudant

et al. 2002

Journal of Lipid Research

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“…Reports such as these suggest that, in addition to serum cholesterol impacting the population kinetics of erythrocytes and platelets, erythrocytes may reciprocally impact serum cholesterol levels. In support of this postulate, in vitro studies indicate that human erythrocytes act as a reservoir of cholesterol for serum lipoproteins, presumably because of their high nonspecifi c cholesterol loading capacity ( 18,19 ).…”

Section: Discussionmentioning

confidence: 95%

Relationship between serum cholesterol and indices of erythrocytes and platelets in the US population

Fessler

Rose

Zhang

et al. 2013

Journal of Lipid Research

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“…In one in vitro study, it was indeed demonstrated that cholesterol efflux from red blood cells was highly correlated with LCAT and CETP activities in postprandial plasma as well as the concentration of secondary acceptors, such as chylomicrons, VLDL, and LDL, but not with the initial acceptor HDL. 43 However, in other in vitro studies, no association between CETP activity in plasma and cholesterol efflux from Fu5AH cells was observed. 44,45 A cholesterol efflux-enhancing role for CETP was also observed in human CETP transgenic mice but not in rabbits.…”

Section: Availability Of Cholesterol Acceptor Particlesmentioning

confidence: 85%

Cholesteryl Ester Transfer Protein (CETP) Inhibition Beyond Raising High-Density Lipoprotein Cholesterol Levels

Klerkx

Harchaoui

Steeg

et al. 2006

ATVB

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Cholesteryl Ester Transfer Protein (CETP) Inhibition Beyond Raising High-Density Lipoprotein Cholesterol Levels Pathways by Which Modulation of CETP Activity May Alter AtherogenesisAnke H.E.M. Klerkx, Karim El Harchaoui, Wim A. van der Steeg, S. Matthijs Boekholdt, Erik S.G. Stroes, John J.P. Kastelein, Jan Albert KuivenhovenAbstract-Raising high-density lipoprotein cholesterol (HDL-C) is a promising strategy in the struggle to prevent cardiovascular disease, and cholesteryl ester transfer protein (CETP) inhibitors have been developed to accomplish this. The first results are encouraging, and, in fact, in rabbits, inhibition of CETP reduces atherosclerosis. Because human data regarding the reduction of atheroma burden require more time, the biochemical mechanisms underlying the putative atheroprotection of CETP inhibitors are currently dissected, and several pathways have emerged. First, CETP inhibition increases HDL-C and reduces low-density lipoprotein cholesterol (LDL-C) levels consistent with CETP lipid transfer activity and its role in reverse cholesterol transport (RCT). This coincides with putative beneficial increases in both HDL and LDL size. However, many aspects regarding the impact of CETP inhibition on the RCT pathway remain elusive, in particular whether the first step concerning cholesterol efflux from peripheral tissues to HDL is influenced. Moreover, the relevance of scavenger receptor BI and consequently the central role of HDL in human RCT is still unclear. Second, CETP inhibition was shown recently to increase antioxidant enzymes associated with HDL, in turn associated with decreased oxidation of LDL. Atheroprotection in man is currently anticipated based on the improvement of these biochemical parameters known to influence atherosclerosis, but final confirmation regarding the impact of CETP inhibition on cardiovascular outcome will have to come from trials evaluating clinical end points. [TGs]) between lipoproteins, and the causes and effects of natural variation in CETP activity, has been the subject of many reviews on CETP and CETP inhibition. 1-6 Therefore, we have chosen to summarize the current understanding of lipoprotein remodeling by CETP ( Figure, 1 and 2). Importantly, in dyslipidemias characterized by increased concentrations of TG-rich particles (mainly very low-density lipoprotein [VLDL] and VLDL remnants), the CE transfer from HDL shifts from LDL toward VLDL, particularly large VLDL1 (Figure, 2). 7,8 This is considered to be atherogenic because CE-enriched VLDLs become substrates for hepatic lipase (HL), resulting in the generation of deleterious small Simplified schematic representation of the effects of CETP inhibition on the RCT pathway and protection against inflammation and oxidation. The numbered flashes indicate impact areas of CETP inhibition, which are further detailed in the respective panels. Flashes with upward or downward arrows indicate upregulation and downregulation, respectively. Black arrows indicate transfer of free cholesterol (FC), CE, or TG; open arrows ...

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Potencies of Lipoproteins in Fasting and Postprandial Plasma to Accept Additional Cholesterol Molecules Released From Cell Membranes

Cited by 21 publications

References 52 publications

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

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

Relationship between serum cholesterol and indices of erythrocytes and platelets in the US population

Cholesteryl Ester Transfer Protein (CETP) Inhibition Beyond Raising High-Density Lipoprotein Cholesterol Levels

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