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Cholesteryl ester transfer protein inhibition: Effect on reverse cholesterol transport?

Rensen, P.C.N. (author), Havekes, L.M. (author), TNO Kwaliteit van Leven (author)

Chemicals / CAS: 2 methylpropanethioic acid s [2 [1 (2 ethylbutyl)cyclohexylcarboxamido]phenyl] ester, 211513-37-0; atorvastatin, 134523-00-5, 134523-03-8; nicotinic acid, 54-86-4, 59-67-6; torcetrapib, 262352-17-0; Carrier Proteins; CETP protein, human; Cholesterol Ester Transfer Proteins; Cholesterol Esters; Cholesterol, HDL; Glycoproteins;...

article 2006

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Apolipoprotein CI overexpression is not a relevant strategy to block cholesteryl ester transfer protein (CETP) activity in CETP transgenic mice

TNO Kwaliteit van Leven (author), Gautier, T. (author), Masson, D. (author), Jong, M.C. (author), Pais De Barros, J.P. (author), Duverneuil, L. (author), Le Guern, N. (author), Deckert, V. (author), Dumont, L. (author), Bataille, A. (author), Zak, Z. (author), Jiang, X.C. (author), Havekes, L.M. (author), Lagrost, L. (author)

ApoCI (apolipoprotein CI) is a potent inhibitor of plasma CETP [CE (cholesteryl ester) transfer protein]. The relevance of apoCI overexpression as a method for CETP blockade in vivo was addressed in the present study in CETPTg/apoCITg mice (mice expressing both human CETP and apoCI). Despite a significant reduction in specific CETP activity in...

article 2005

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Cholesterol 7α-Hydroxylase Deficiency in Mice on an APOE*3-Leiden Background Impairs Very-Low-Density Lipoprotein Production

Post, S.M. (author), Groenendijk, M. (author), Solaas, K. (author), Rensen, P.C.N. (author), Princen, H.M.G. (author), TNO Preventie en Gezondheid (author)

Objective-Cholesterol 7α-hydroxylase (cyp7a1) catalyzes the rate-limiting step in conversion of cholesterol to bile acids. To study the relationship between bile acid biosynthesis and triglyceride metabolism, we cross-bred mice lacking cyp7a1 on a hyperlipidemic APOE*3-Leiden background. Methods and Results-Female mice received a chow or...

article 2004

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Effect of Moderate Alcohol Consumption on Parameters of Reverse Cholesterol Transport in Postmenopausal Women

Sierksma, A. (author), Vermunt, S.H.F. (author), Lankhuizen, I.M. (author), van der Gaag, M.S. (author), Scheek, L.M. (author), Grobbee, D.E. (author), van Tol, A. (author), Hendriks, H.F.J. (author), TNO Voeding (author)

Background: Alcohol consumption is associated with increased high-density lipoprotein (HDL) cholesterol levels. One of the main antiatherogenic functions of HDL is reverse cholesterol transport. Three early steps of reverse cholesterol transport are (1) cellular cholesterol efflux, (2) plasma cholesterol esterification (EST), and (3) cholesteryl...

article 2004

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Apolipoprotein CI deficiency markedly augments plasma lipoprotein changes mediated by human cholesteryl ester transfer protein (CETP) in CETP transgenic/apoCI-knocked out mice

Gaubius Instituut TNO (author), Gautier, T. (author), Masson, D. (author), Jong, M.C. (author), Duverneuil, L. (author), Guern, N.L. (author), Deckert, V. (author), de Barros, J.P.P. (author), Dumont, L. (author), Bataille, A. (author), Zak, Z. (author), Jiang, X.C. (author), Tall, A.R. (author), Havekes, L.M. (author), Lagrost, L. (author)

Transgenic mice expressing human cholesteryl ester transfer protein (HuCETPTg mice) were crossed with apolipoprotein CI-knocked out (apoCI-KO) mice. Although total cholesterol levels tended to be reduced as the result of CETP expression in HuCETPTg heterozygotes compared with C57BL6 control mice (-13%, not significant), a more pronounced...

article 2002

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Alcohol consumption stimulates early steps in reverse cholesterol transport

Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author), van der Gaag, M.S. (author), van Tol, A. (author), Vermunt, S.H.F. (author), Scheek, L.M. (author), Schaafsma, G. (author), Hendriks, H.F.J. (author)

Alcohol consumption is associated with increased HDL cholesterol levels, which may indicate stimulated reverse cholesterol transport. The mechanism is, however, not known. The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol pathway: cellular cholesterol efflux and plasma...

article 2001

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Apolipoprotein E is resistant to intracellular degradation in vitro and in vivo. Evidence for retroendocytosis

Gaubius instituut TNO (author), Rensen, P.C.N. (author), Jong, M.C. (author), van Vark, L.C. (author), van der Boom, H. (author), Hendriks, W.L. (author), van Berkel, T.J.C. (author), Biessen, E.A.L. (author), Havekes, L.M. (author)

Apolipoprotein E (apoE) is an important determinant for the uptake of triglyceride-rich lipoproteins and emulsions by the liver, but the intracellular pathway of apoE following particle internalization is poorly defined. In the present study, we investigated whether retroendocytosis is a unique feature of apoE as compared with apoB by studying...

article 2000

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Acyl-coenzyme A:cholesterol acyltransferase inhibitor, avasimibe, stimulates bile acid synthesis and cholesterol 7α-hydroxylase in cultured rat hepatocytes and in vivo in the rat

Post, S.M. (author), Paul Zoeteweij, J. (author), Bos, M.H.A. (author), de Wit, E.C.M. (author), Havinga, R. (author), Kuipers, F. (author), Princen, H.M.G. (author), Gaubius instituut TNO (author)

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitors are currently in clinical development as potential lipid-lowering and antiatherosclerotic agents. We investigated the effect of avasimibe (C1- 1011), a novel ACAT inhibitor, on bile acid synthesis and cholesterol 7α- hydroxylase in cultured rat hepatocytes and rats fed different diets...

article 1999

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Macrophage specific overexpression of the human macrophage scavenger receptor in transgenic mice, using a 180-kb yeast artificial chromosome, leads to enhanced foam cell formation of isolated peritoneal macrophages

de Winther, M.P.J. (author), van Dijk, K.W. (author), van Vlijmen, B.J.M. (author), Gijbels, M.J.J. (author), Heus, J.J. (author), Wijers, E.R. (author), van den Bos, A.C. (author), Breuer, M. (author), Frants, R.R. (author), Havekes, L.M. (author), Hofker, M.H. (author), Gaubius instituut TNO (author)

Macrophage scavenger receptors class A (MSR) are thought to play an important role in atherogenesis by mediating the unrestricted uptake of modified lipoproteins by macrophages in the vessel wall leading to foam cell formation. To investigate the in vivo role of the MSR in this process, a transgenic mouse model expressing both isoforms of the...

article 1999

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Moderate doses of alcoholic beverages with dinner and postprandial high density lipoprotein composition

Hendriks, H.F.J. (author), Veenstra, J. (author), van Tol, A. (author), Groener, J.E.M. (author), Schaafsma, G. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. In this study, postprandial changes in plasma lipids, high-density lipoprotein (HDL) composition and cholesteryl ester transfer protein (CETP) and lecithin: cholesterol acyltransferase (LCAT) activity levels were investigated in response to moderate alcohol...

article 1998

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Effect of methylglyoxal on the physico-chemical and biological properties of low-density lipoprotein

Schalkwijk, C.G. (author), Vermeer, M.A. (author), Stehouwer, C.D.A. (author), te Koppele, J. (author), Princen, H.M.G. (author), van Hinsbergh, V.W.M. (author), Gaubius Instituut TNO (author)

In patients with diabetes, non-enzymatic glycation of low-density lipoprotein (LDL) has been suggested to be involved in the development of atherosclerosis. α-Dicarbonyl compounds were identified as intermediates in the non-enzymatic glycation and increased levels were reported in patients with diabetes. We studied the effect of the α-dicarbonyl...

article 1998

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Adenovirus mediated overexpression of human phospholipid transfer protein alters plasma HDL levels in mice

Gaubius Instituut TNO (author), Ehnholm, S. (author), van Dijk, K.W. (author), van Hof, B. (author), van Zee, A.D. (author), Olkkonen, V.M. (author), Jauhiainen, M. (author), Hofker, M. (author), Havekes, L. (author), Ehnholm, C. (author)

To study the function of plasma phospholipid transfer protein (PLTP) in vivo, a liver directed adenoviral gene transfer system was used to overexpress human PLTP in mice. For the experiments, two strains of mice, wild type (C57/B1) and mice transgenic for the human apoA-I gene (HuApoA- ITg), were utilized. Five days after injection of the...

article 1998

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Interactions between lifestyle-related factors and the ApoE polymorphism on plasma lipids and apolipoproteins: The ears study

Boer, J.M.A. (author), Ehnholm, C. (author), Menzel, H.J. (author), Havekes, L.M. (author), Rosseneu, M. (author), O'Reilly, D.S.J. (author), Tiret, L. (author), Gaubius Instituut TNO (author)

To elucidate how the apolipoprotein (apo)E polymorphism and modifiable factors interact in explaining plasma lipid and apolipoprotein levels, we studied 1448 young adults (18 to 26 years old), participating in the European Atherosclerosis Research Study (EARS). Venous blood was collected after an overnight fast. Modifiable factors, eg, body mass...

article 1997

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Cafestol, the cholesterol-raising factor in boiled coffee, suppresses bile acid synthesis by downregulation of cholesterol 7α-hydroxylase and sterol 27-hydroxylase in rat hepatocytes

Post, S.M. (author), de Wit, E.C.M. (author), Princen, H.M.G. (author), Gaubius Instituut TNO (author)

Consumption of boiled coffee raises serum cholesterol levels in humans. The diterpenes cafestol and kahweol in boiled coffee have been found to be responsible for the increase. To investigate the biochemical background of this effect, we studied the effects of cafestol and a mixture of cafestol/kahweol/isokahweol (48:47:5 w/w) on bile acid...

article 1997

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Uptake by J774 macrophages of very-low-density lipoproteins isolated from apoE-deficient mice is mediated by a distinct receptor and stimulated by lipoprotein lipase

Hendriks, W.L. (author), de Sman van der - Beer, F. (author), van Vlijmen, B.J.M. (author), van Vark, L.C. (author), Hofker, M.H. (author), Havekes, L.M. (author), TNO Preventie en Gezondheid (author)

Apolipoprotein (apo) E-deficient mice display marked accumulation in the plasma of VLDL deficient in both apoE and apoBl00 but containing apoB48, apoA-1, apoCs, and apoA-IV. Since apoE-deficient mice develop severe atherosclerotic lesions with lipid-laden macrophages, we reasoned that the uptake of lipoproteins by intimal macrophages can take...

article 1997

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Lipoprotein lipase stimulates the binding and uptake of moderately oxidized low-density lipoprotein by J774 macrophages

Gaubius instituut TNO (author), Hendriks, W.L. (author), van der Boom, H. (author), van Vark, L.C. (author), Havekes, L.M. (author)

Lipoprotein lipase (LPL) stimulates the uptake of low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) in different cell types, including macrophages, through bridging of LPL between lipoproteins and extracellular heparan sulphate proteoglycans (HSPG). Because macrophages produce LPL and because modified lipoproteins are present...

article 1996

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Vastatins inhibit cholesterol ester accumulation in human monocyte-derived macrophages

Kempen, H.J.M. (author), Vermeer, M. (author), de Wit, E. (author), Havekes, L.M. (author), Gaubius instituut TNO (author)

Human monocyte-derived macrophages were incubated for 48 hours in Medium 199 with 1% human serum albumin, and with 100 μg acetyl low density lipoprotein (LDL) or β-very low density lipoprotein (β-VLDL), with or without various concentrations of compactin, lovastatin, simvastatin, or pravastatin. The mass of free (FC) and esterified (CE)...

article 1991

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Effect of infusion of 'tris-galactosyl-cholesterol' on plasma cholesterol, clearance of lipoprotein cholesteryl esters, and biliary secretion in the rat

Gaubius instituut TNO (author), Kempen, H.J. (author), Kuipers, F. (author), van Berkel, T.J.C. (author), Vonk, R.J. (author)

As shown by us previously (van Berkel et al. 1985. J. Biol. Chem. 260: 2694-2699 and van Berkel et al. 1985. J. Biol. Chem. 260: 12203-12207) the clearance of both low density lipoproteins (LDL) and high density lipoproteins (HDL) from the blood can be greatly enhanced by pretreatment of these lipoproteins with a tris-galactosylated cholesterol...

article 1987

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Lipoprotein secretion by isolated rat hepatocytes: Characterization of the lipid-carrying particles and modulation of their release

Gaubius instituut TNO (author), Kempen, H.J.M. (author)

Lipoprotein production by freshly isolated rat hepatocytes in suspension was studied during short (1-3 hr) incubation periods. The heaptocytes release very low density (91.10 g/ml). These particles with higher densities have not been positively identified; the latter group is dissimilar to the high density lipoprotein, which occurs in rat liver...

article 1980