Determinants of plasma HDL concentrations and reverse cholesterol transport

Lewis, Gary F.

doi:10.1097/01.hco.0000231405.76930.a0

Cited by 74 publications

(47 citation statements)

References 76 publications

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“…In addition, the displacement of dietary carbohydrates by monounsaturated fat is likely to result in less carbohydrateinduced hepatic synthesis of very-low-density lipoprotein triglyceride. 28 The resulting lower concentration of very-low-density lipoprotein triglyceride, although not significant in the present study, may attenuate the impact of cholesteryl ester transfer protein in depleting cholesteryl ester in HDL, 29,30 thereby contributing to a rise in plasma concentration of HDL cholesterol. It might also be predicted that the resulting triglyceride-poor, cholesterylester-rich HDL would be less rapidly lost from the circulation by tissue uptake than a triglyceride-rich cholesteryl-ester-poor particle.…”

Section: Discussionmentioning

confidence: 78%

Adding monounsaturated fatty acids to a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia

Jenkins¹,

Chiavaroli²,

Wong³

et al. 2010

Canadian Medical Association Journal

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Strategies that combine cholesterol-lowering foods or food components such as viscous fibres and plant sterols have been recommended to enhance the effectiveness of therapeutic diets low in saturated fat and cholesterol.1,2 Such dietary combinations (known as dietary portfolios) have resulted in substantial reductions in low-density lipoprotein (LDL) cholesterol 3 and its apolipoprotein (apolipoprotein B), but the beneficial effects on high-density lipoprotein (HDL) cholesterol and its apolipoprotein (apolipoprotein AI) have been less apparent. 4 Low concentrations of HDL cholesterol and apolipoprotein AI in the plasma and an elevated ratio of total to HDL cholesterol are recognized risk factors for cardiovascular disease.5−9 Thus, dietary strategies that both lower total and LDL cholesterol and raise HDL cholesterol should have broad application. One method for increasing HDL cholesterol appears to be the use of monounsaturated fat, a key constituent of the Mediterranean diet, particularly when monounsaturated fat replaces dietary carbohydrates.10,11 Furthermore, increased intake of monounsaturated fat, through increased consumption of nuts and vegetable oil, has been associated with a reduced incidence of cardiovascular disease in cohort studies. 12,13We compared the effect on serum lipids of substituting 13.0% of total calories as carbohydrate with monounsaturated fatty acid in a dietary portfolio that has previously been shown, under controlled conditions, to be effective in lowering LDL cholesterol (by 28%) and the ratio of total to HDL cholesterol (by 24%).3 These reductions are similar to those seen with lovastatin 20 mg/d taken with the control diet. Background: Higher intake of monounsaturated fat may raise high-density lipoprotein (HDL) cholesterol without raising low-density lipoprotein (LDL) cholesterol. We tested whether increasing the monounsaturated fat content of a diet proven effective for lowering LDL cholesterol (dietary portfolio) also modified other risk factors for cardiovascular disease, specifically by increasing HDL cholesterol, lowering serum triglyceride and further reducing the ratio of total to HDL cholesterol.

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Section: Discussionmentioning

confidence: 78%

Adding monounsaturated fatty acids to a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia

Jenkins¹,

Chiavaroli²,

Wong³

et al. 2010

Canadian Medical Association Journal

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“…In experimental animals, both overexpression ( 5, 12 ) as well as loss-of-function models ( 13-15 ) have established EL to be a negative regulator of plasma HDL cholesterol levels by increasing HDL catabolism. Moreover, accumulating evidence points to a comparable role of EL in human HDL metabolism (15)(16)(17).Consistent with the role of HDL in RCT, HDL is thought to represent a preferred source of sterols that are subsequently secreted into the bile ( 3,4,18,19 ). Currently, no data are available regarding the effect of an acute decrease of plasma HDL cholesterol levels on biliary sterol excretion caused by a single physiologically relevant stimulus.…”

mentioning

confidence: 96%

“…This protective effect of HDL is largely ascribed to the role of this lipoprotein in reverse cholesterol transport (RCT), a process comprising the movement of excess cholesterol from the periphery back to the liver for subsequent secretion into the bile ( 3,4 ). Within the plasma compartment, substantial remodeling of HDL particles occurs.…”

mentioning

confidence: 99%

Hepatic SR-BI, not endothelial lipase, expression determines biliary cholesterol secretion in mice

Wiersma

Gatti

Nijstad

et al. 2009

Journal of Lipid Research

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vascular disease ( 1,2 ). This protective effect of HDL is largely ascribed to the role of this lipoprotein in reverse cholesterol transport (RCT), a process comprising the movement of excess cholesterol from the periphery back to the liver for subsequent secretion into the bile ( 3,4 ). Within the plasma compartment, substantial remodeling of HDL particles occurs. A factor exerting a major impact in this regard is endothelial lipase (EL).EL has recently been identifi ed as a member of the triacylglycerol lipase gene family. It is expressed in endothelial cells as well as in macrophages and hepatocytes ( 5, 6 ). Remarkably, EL possesses merely phospholipase activity ( 7 ). EL expression is upregulated in vitro by proinfl ammatory stimuli ( 8, 9 ), and EL plasma levels correlate with the levels of proinfl ammatory cytokines in human populations ( 10, 11 ). In experimental animals, both overexpression ( 5, 12 ) as well as loss-of-function models ( 13-15 ) have established EL to be a negative regulator of plasma HDL cholesterol levels by increasing HDL catabolism. Moreover, accumulating evidence points to a comparable role of EL in human HDL metabolism (15)(16)(17).Consistent with the role of HDL in RCT, HDL is thought to represent a preferred source of sterols that are subsequently secreted into the bile ( 3,4,18,19 ). Currently, no data are available regarding the effect of an acute decrease of plasma HDL cholesterol levels on biliary sterol excretion caused by a single physiologically relevant stimulus. This study aimed to test the hypothesis that an acute, substantial decrease of plasma HDL cholesterol levels by EL overexpression impacts liver cholesterol metabolism and biliary cholesterol secretion. Our data demonstrate that in wild-type mice, virtual elimination of HDL cholesterol by Abstract High density lipoprotein cholesterol is thought to represent a preferred source of sterols secreted into bile following hepatic uptake by scavenger receptor class B type I (SR-BI). The present study aimed to determine the metabolic effects of an endothelial lipase (EL)-mediated stimulation of HDL cholesterol uptake on liver lipid metabolism and biliary cholesterol secretion in wild-type, SR-BI knockout, and SR-BI overexpressing mice. In each model, injection of an EL expressing adenovirus decreased plasma HDL cholesterol ( P < 0.001) whereas hepatic cholesterol content increased ( P < 0.05), translating into decreased expression of sterol-regulatory element binding protein 2 (SREBP2) and its target genes HMG-CoA reductase and LDL receptor (each P < 0.01). Biliary cholesterol secretion was dependent on hepatic SR-BI expression, being decreased in SR-BI knockouts ( P < 0.001) and increased following hepatic SR-BI overexpression ( P < 0.001). However, in each model, biliary secretion of cholesterol, bile acids, and phospholipids as well as fecal bile acid and neutral sterol content, remained unchanged in response to EL overexpression. Importantly, hepatic ABCG5/G8 expression did not correlate with biliary cholesterol secret...

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“…Apolipoprotein A-I (ApoA-I) is a major protein component of HDL. In adult organisms, ApoA-I is synthesized and secreted by the liver and small intestine (5,6). ATP-binding cassette transporter A1 (ABCA1) is the major transporter for cholesterol efflux from peripheral tissues and lipidation of ApoA-I in the liver, and it is the key determinant of plasma HDL levels, as shown in Tangier disease and ABCA1-deficient mice (7 -9).…”

Section: Introductionmentioning

confidence: 99%

Pitavastatin Increases ABCA1 Expression by Dual Mechanisms: SREBP2-Driven Transcriptional Activation and PPARα-Dependent Protein Stabilization but Without Activating LXR in Rat Hepatoma McARH7777 Cells

et al. 2011

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Abstract. Hepatic ATP-binding cassette transporter A1 (ABCA1) plays a key role in high-density lipoprotein (HDL) production by apolipoprotein A-I (ApoA-I) lipidation. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, increase ABCA1 mRNA levels in hepatoma cell lines, but their mechanism of action is not yet clear. We investigated how statins increase ABCA1 in rat hepatoma McARH7777 cells. Pitavastatin, atorvastatin, and simvastatin increased total ABCA1 mRNA levels, whereas pravastatin had no effect. Pitavastatin also increased ABCA1 protein. Hepatic ABCA1 expression in rats is regulated by both liver X receptor (LXR) and sterol regulatory element-binding protein (SREBP2) pathways. Pitavastatin repressed peripheral type ABCA1 mRNA levels and its LXR-driven promoter, but activated the liver-type SREBPdriven promoter, and eventually increased total ABCA1 mRNA expression. Furthermore, pitavastatin increased peroxisome proliferator-activated receptor α (PPARα) and its downstream gene expression. Knockdown of PPARα attenuated the increase in ABCA1 protein, indicating that pitavastatin increased ABCA1 protein via PPARα activation, although it repressed LXR activation. Furthermore, the degradation of ABCA1 protein was retarded in pitavastatin-treated cells. These data suggest that pitavastatin increases ABCA1 protein expression by dual mechanisms: SREBP2-mediated mRNA transcription and PPARα-mediated ABCA1 protein stabilization, but not by the PPAR-LXR-ABCA1 pathway.

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Determinants of plasma HDL concentrations and reverse cholesterol transport

Cited by 74 publications

References 76 publications

Adding monounsaturated fatty acids to a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia

Adding monounsaturated fatty acids to a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia

Hepatic SR-BI, not endothelial lipase, expression determines biliary cholesterol secretion in mice

Pitavastatin Increases ABCA1 Expression by Dual Mechanisms: SREBP2-Driven Transcriptional Activation and PPARα-Dependent Protein Stabilization but Without Activating LXR in Rat Hepatoma McARH7777 Cells

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