Opposite Effects of Cholesteryl Ester Transfer Protein and Phospholipid Transfer Protein on the Size Distribution of Plasma High Density Lipoproteins

Lagrost, Laurent; Athias, Anne; Herbeth, Bernard; Guyard-Dangremont, Valérie; Artur, Yves; Paille, F.; Gambert, Philippe; Lallemant, Christian

doi:10.1074/jbc.271.32.19058

Cited by 78 publications

(43 citation statements)

References 48 publications

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“…Therefore, we conclude that the large lipoprotein particle found in hPLTPtg/hApoAItg mice is a very large, cholesterol-enriched subspecies of HDL displaying LDL density. In vitro HDL conversion studies demonstrated that human PLTP is able to promote the conversion of a homogenous population of human HDL 3 particles into a new population with an increased average size via particle fusion (34)(35)(36). Earlier, a small increase in HDL size was observed in a human PLTP/human apoA-I double transgenic mouse model displaying a slightly increased PLTP activity (37).…”

Section: Discussionmentioning

confidence: 99%

Atherogenic, enlarged, and dysfunctional HDL in human PLTP/apoA-I double transgenic mice

Moerland

Samyn

Gent

et al. 2007

Journal of Lipid Research

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In low density lipoprotein receptor (LDLR)-deficient mice, overexpression of human plasma phospholipid transfer protein (PLTP) results in increased atherosclerosis. PLTP strongly decreases HDL levels and might alter the antiatherogenic properties of HDL particles. To study the potential interaction between human PLTP and apolipoprotein A-I (apoA-I), double transgenic animals (hPLTPtg/ hApoAItg) were compared with hApoAItg mice. PLTP activity was increased 4.5-fold. Plasma total cholesterol and phospholipid were decreased. Average HDL size (analyzed by gel filtration) increased strongly, hPLTPtg/hApoAItg mice having very large, LDL-sized, HDL particles. Also, after density gradient ultracentrifugation, a substantial part of the apoA-I-containing lipoproteins in hPLTPtg/hApoAItg mice was found in the LDL density range. In cholesterol efflux studies from macrophages, HDL isolated from hPLTPtg/ hApoAItg mice was less efficient than HDL isolated from hApoAItg mice. Furthermore, it was found that the largest subfraction of the HDL particles present in hPLTPtg/hApoAItg mice was markedly inferior as a cholesterol acceptor, as no labeled cholesterol was transferred to this fraction. In an LDLR-deficient background, the human PLTP-expressing mouse line showed a 2.2-fold increased atherosclerotic lesion area. These data demonstrate that the action of human PLTP in the presence of human apoA-I results in the formation of a dysfunctional HDL subfraction, which is less efficient in the uptake of cholesterol from cholesterol-laden macrophages.-Moerland, M., H. Samyn, T. van Gent, M. Jauhiainen, J. Metso, R. The incidence of coronary heart disease shows a strong inverse relationship with the concentration of plasma HDL (1). Therefore, HDL is believed to have antiatherogenic properties, which are attributed to its effects on endothelial cells, its antioxidant activity, and its role in reverse cholesterol transport, a pathway in which peripheral cellular cholesterol is transported to the liver (2-4). One important determinant of the plasma HDL concentration is phospholipid transfer protein (PLTP) activity. During lipolysis, PLTP transfers phospholipids from apolipoprotein Bcontaining lipoproteins to HDL (5). Furthermore, PLTP acts as an HDL conversion factor by remodeling HDL to produce large particles and small lipid-poor particles, known as preb-HDL (6-9). The latter HDL subfraction is a very efficient acceptor of cellular cholesterol. In this way, PLTP plays an important role in the early steps of reverse cholesterol transport (10-12).Although the involvement of PLTP in the cellular efflux of cholesterol and phospholipids is potentially antiatherogenic, different in vivo studies showed that an increase in plasma PLTP activity is associated with decreased HDL cholesterol levels (9, 13, 14) and increased atherosclerotic lesion development (15-17). The PLTP-dependent decrease in HDL levels was explained by an accelerated HDL catabolism (13). In addition to its effect on HDL cholesterol levels, PLTP may alter the antiathe...

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Section: Discussionmentioning

confidence: 99%

Atherogenic, enlarged, and dysfunctional HDL in human PLTP/apoA-I double transgenic mice

Moerland

Samyn

Gent

et al. 2007

Journal of Lipid Research

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“…An increase in NEFA is also a characteristic of other conditions associated with an increase in PLTP. PLTP activity is elevated in alcoholics, who demonstrate increased NEFA concentrations, and PLTP decreases upon withdrawal (33,34). PLTP activity decreases with the administration of Acipimox, which is thought to inhibit hormone-sensitive lipase and thus decrease NEFA release from adipose tissue (35).…”

Section: Discussionmentioning

confidence: 99%

PLTP activity decreases with weight loss

Murdoch

Kahn

Albers

et al. 2003

Journal of Lipid Research

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“…The sphingomyelin:lecithin ratio in the HDL was measured by liquid chromatography/mass spectrometry as previously described [7]. 7.21-7.76 nm) were determined by polyacrylamide gradient gel electrophoresis as previously described [8].…”

Section: Methodsmentioning

confidence: 99%

HDL particles from type 1 diabetic patients are unable to reverse the inhibitory effect of oxidised LDL on endothelium-dependent vasorelaxation

et al. 2007

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Aims/hypothesis In healthy individuals, HDL can counteract the inhibition of vasorelaxation induced by oxidised LDL. Several abnormalities such as increased size, glycation and decreased paraoxonase activity have been reported for HDL from type 1 diabetic patients. Thus, we hypothesised that the ability of HDL to protect vessels against impairments of vasorelaxation would be decreased in these patients. Methods We compared the ability of HDL from 18 type 1 diabetic patients and 12 control participants to counteract the inhibition of endothelium-dependent relaxation induced by oxidised LDL on rabbit aorta rings. Results Serum triacylglycerol and total cholesterol, LDLand HDL-cholesterol were similar in type 1 diabetic and control participants. Fasting glycaemia and the HDLfructosamine level were higher in diabetic patients than in controls (9.06±3.55 vs 5.27±0.23 mmol/l, p<0.005; and 10.2±3.2 vs 7.7±2.5 μmol/g protein, p<0.05, respectively). HDL composition, size and paraoxonase activity were similar in both groups. HDL from controls reduced the inhibitory effect of oxidised LDL on maximal relaxation (E max ; 79.3± 11.8 vs 66.4±11.7%, p<0.05), whereas HDL from type 1 diabetic patients had no effect (E max =70.6±17.4 vs 63.9± 17.2%, NS). In type 1 diabetic patients, E max was not correlated with glycaemia or the HDL-fructosamine level. Conclusions/interpretation HDL particles from type 1 diabetic patients do not protect against inhibition of endothelium-dependent vasorelaxation induced by oxidised LDL, in contrast to HDL particles from healthy individuals. This defect cannot be explained by abnormalities in HDL composition, size or paraoxonase activity, and may contribute to the early development of atherosclerotic lesions in type 1 diabetic patients.

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Opposite Effects of Cholesteryl Ester Transfer Protein and Phospholipid Transfer Protein on the Size Distribution of Plasma High Density Lipoproteins

Cited by 78 publications

References 48 publications

Atherogenic, enlarged, and dysfunctional HDL in human PLTP/apoA-I double transgenic mice

Atherogenic, enlarged, and dysfunctional HDL in human PLTP/apoA-I double transgenic mice

PLTP activity decreases with weight loss

HDL particles from type 1 diabetic patients are unable to reverse the inhibitory effect of oxidised LDL on endothelium-dependent vasorelaxation

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