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Apolipoprotein CI knock-out mice display impaired memory functions

Berbée, J.F.P. (author), Abildayeva, K. (author), Blokland, A. (author), Jansen, P.J. (author), Lütjohann, D. (author), Gautier, T. (author), Sijbrands, E. (author), Prickaerts, J. (author), Hadfoune, M. (author), Ramaekers, F.C.S. (author), Kuipers, F. (author), Rensen, P.C.N. (author)

The e4 allele of apolipoprotein E (APOE4), which is a well established genetic risk factor for development of Alzheimer's disease (AD), is in genetic disequilibrium with the H2 allele of apolipoprotein C1 (APOC1), giving rise to increased expression of apoC-I. This raises the possibility that the H2 allele of APOC1, either alone or in...

article 2011

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Wet-wrap treatment using dilutions of tacrolimus ointment and fluticasone propionate cream in human APOC1 (+/+) mice with atopic dermatitis

Oranje, A.P. (author), Verbeek, R. (author), Verzaal, P. (author), Haspels, I. (author), Prens, E. (author), Nagelkerken, L. (author), TNO Kwaliteit van Leven (author)

Background: Wet-wrap treatment (WWT) with diluted topical steroids is widely used in atopic dermatitis (AD). Mice with transgenic overexpression of human apolipoprotein C1 (APOC1) in the liver and the skin are not only characterized by hyperlipidaemia and raised IgE levels, but also by pruritic dermatitis and a disturbed skin barrier function,...

article 2009

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Apolipoprotein CI inhibits scavenger receptor BI and increases plasma HDL levels in vivo

de Haan, W. (author), Out, R. (author), Berbée, J.F.P. (author), van der Hoogt, C.C. (author), Dijk, K.W.v. (author), van Berkel, T.J.C. (author), Romijn, J.A. (author), Wouter Jukema, J. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)

Apolipoprotein CI (apoCI) has been suggested to influence HDL metabolism by activation of LCAT and inhibition of HL and CETP. However, the effect of apoCI on scavenger receptor BI (SR-BI)-mediated uptake of HDL-cholesteryl esters (CE), as well as the net effect of apoCI on HDL metabolism in vivo is unknown. Therefore, we evaluated the effect of...

article 2008

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Plasma apolipoprotein CI protects against mortality from infection in old age

Berbée, J.F.P. (author), Mooijaart, S.P. (author), de Craen, A.J.M. (author), Havekes, L.M. (author), van Heemst, D. (author), Rensen, P.C.N. (author), Westendorp, R.G.J. (author), TNO Kwaliteit van Leven (author)

The high-density lipoprotein (HDL) constituent apolipoprotein CI (apoCI) protects mice against mortality in bacterial sepsis. We assessed whether high plasma apoCI levels protect against mortality from infection in humans. We determined plasma levels of apoCI, lipids, and C-reactive protein in 85-year-old participants of the prospective...

article 2008

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Preoperative apolipoprotein CI levels correlate positively with the proinflammatory response in patients experiencing endotoxemia following elective cardiac surgery

Schippers, E.F. (author), Berbée, J.F.P. (author), van Disseldorp, I.M. (author), Versteegh, M.I.M. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), van Dissel, J.T. (author), TNO Kwaliteit van Leven (author)

Objective: Experimental models show that apolipoprotein CI (apoCI) binds and enhances the inflammatory response to endotoxin. We studied in patients undergoing cardiopulmonary bypass surgery (CPB) and experiencing endotoxemia during reperfusion whether plasma apoCI levels correlate with the inflammatory response and perioperative cytokine...

article 2008

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Plasma apolipoprotein CI correlates with increased survival in patients with severe sepsis

Berbée, J.F.P. (author), van der Hoogt, C.C. (author), de Haas, C.J.C. (author), van Kessel, K.P.M. (author), Dallinga-Thie, G.M. (author), Romijn, J.A. (author), Havekes, L.M. (author), van Leeuwen, H.J. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)

Objective: We recently reported that apolipoprotein CI (apoCI) protects against the development of murine bacterial sepsis. We now examined the time course of plasma apoCI levels in survivors and non-survivors of severe sepsis. Design: Prospective study in patients meeting predefined criteria for severe sepsis. Setting: University hospital...

article 2008

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Development of atopic dermatitis in mice transgenic for human apolipoprotein C1

Nagelkerken, L. (author), Verzaal, P. (author), Lagerweij, T. (author), Persoon-Deen, C. (author), Berbee, J.F.P. (author), Prens, E.P. (author), Havekes, L.M. (author), Oranje, A.P. (author), TNO Kwaliteit van Leven (author)

Mice with transgenic expression of human apolipoprotein C1 (APOC1) in liver and skin have strongly increased serum levels of cholesterol, triglycerides, and free fatty acids, indicative of a disturbed lipid metabolism. Importantly, these mice display a disturbed skin barrier function, evident from increased transepidermal water loss, and...

article 2008

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ApoE2-associated hypertriglyceridemia is ameliorated by increased levels of apoA-V but unaffected by apoC-III deficiency

TNO Kwaliteit van Leven (author), Gerritsen, G. (author), van der Hoogt, C.C. (author), Schaap, F.G. (author), Voshol, P.J. (author), Kypreos, K.E. (author), Maeda, N. (author), Groen, A.K. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), van Dijk, K.W. (author)

Apolipoprotein E2 (apoE2)-associated hyperlipidemia is characterized by a disturbed clearance of apoE2-enriched VLDL remnants. Because excess apoE2 inhibits LPL-mediated triglyceride (TG) hydrolysis in vitro, we in vestigated whether direct or indirect stimulation of LPL activity in vivo reduces the apoE2-associated hypertriglyc-eridemia. Here,...

article 2008

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Human apolipoprotein C-I expression in mice impairs learning and memory functions

TNO Kwaliteit van Leven (author), Abildayeva, K. (author), Berbée, J.F.P. (author), Blokland, A. (author), Jansen, P.J. (author), Hoek, F.J. (author), Meijer, O. (author), Lütjohann, D. (author), Gautier, T. (author), Pillot, T. (author), Vente, J.de (author), Havekes, L.M. (author), Ramaekers, F.C.S. (author), Kuipers, F. (author), Rensen, P.C.N. (author), Mulder, M. (author)

The H2 allele of APOC1, giving rise to increased gene expression of apolipoprotein C-I (apoC-I), is in genetic disequilibrium with the APOE4 allele and may provide a major risk factor for Alzheimer's disease (AD). We found that apoC-I protein is present in astrocytes and endothelial cells within hippocampal regions in both human control and AD...

article 2008

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Apolipoprotein CI aggravates atherosclerosis development in ApoE-knockout mice despite mediating cholesterol efflux from macrophages

Westerterp, M. (author), van Eck, M. (author), de Haan, W. (author), Offerman, E.H. (author), van Berkel, T.J.C. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)

Objective: Apolipoprotein CI (apoCI) is expressed in the liver and in macrophages, and has several roles in lipid metabolism. Since macrophage apoCI expression might affect macrophage lipid homeostasis and atherosclerotic lesion development locally in the arterial wall, we investigated the effect of both systemic and macrophage apoCI on...

article 2007

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Hepatic lipid accumulation in apolipoprotein C-I-deficient mice is potentiated by cholesteryl ester transfer protein

TNO Kwaliteit van Leven (author), Gautier, T. (author), Tietge, U.J.F. (author), Boverhof, R. (author), Perton, F.G. (author), Le Guern, N. (author), Masson, D. (author), Rensen, P.C.N. (author), Havekes, L.M. (author), Lagrost, L. (author), Kuipers, F. (author)

The impact of apolipoprotein C-I (apoC-I) deficiency on hepatic lipid metabolism was addressed in mice in the presence or the absence of cholesteryl ester transfer protein (CETP). In addition to the expected moderate reduction in plasma cholesterol levels, apoCIKO mice showed significant increases in the hepatic content of cholesteryl esters (...

article 2007

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Apolipoprotein C-I is crucially involved in lipopolysaccharide-induced atherosclerosis development in apolipoprotein E-knockout mice

TNO Kwaliteit van Leven (author), Westerterp, M. (author), Berbée, J.F.P. (author), Pires, N.M.M. (author), van Mierlo, G.J.D. (author), Kleemann, R. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)

BACKGROUND - Lipopolysaccharide (LPS), which is released from Gram-negative bacteria on multiplication or lysis, aggravates atherosclerosis in humans and rodents by inducing inflammation via toll-like receptors. Because apolipoprotein C-I (apoCI) enhances the LPS-induced inflammatory response in macrophages in vitro and in mice, we investigated...

article 2007

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Apolipoprotein C-I binds free fatty acids and reduces their intracellular esterification

TNO Kwaliteit van Leven (author), Westerterp, M. (author), Berbée, J.F.P. (author), Delsing, D.J.M. (author), Jong, M.C. (author), Gijbels, M.J.J. (author), Dahlmans, V.E.H. (author), Offerman, E.H. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)

Mice that overexpress human apolipoprotein C-I (apoC-I) homozygously (APOC1+/+ mice) are protected against obesity and show cutaneous abnormalities. Although these effects can result from our previous observation that apoC-I inhibits FFA generation by LPL, we have also found that apoC-I impairs the uptake of a FFA analog in adipose tissue. In...

article 2007

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Apolipoprotein CI stimulates the response to lipopolysaccharide and reduces mortality in gram-negative sepsis.

Berbée, J.F. (author), van der Hoogt, C.C. (author), Kleemann, R. (author), Schippers, E.F. (author), Kitchens, R.L. (author), van Dissel, J.T. (author), Bakker-Woudenberg, I.A. (author), Havekes, L.M. (author), Rensen, P.C. (author), TNO Kwaliteit van Leven (author)

Gram-negative sepsis is a major death cause in intensive care units. Accumulating evidence indicates the protective role of plasma lipoproteins such as high-density lipoprotein (HDL) in sepsis. It has recently been shown that septic HDL is almost depleted from apolipoprotein CI (apoCI), suggesting that apoCI may be a protective factor in sepsis....

article 2006

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Endogenous apoC-I increases hyperlipidemia in apoE-knockout mice by stimulating VLDL production and inhibiting LPL

TNO Kwaliteit van Leven (author), Westerterp, M. (author), de Haan, W. (author), Berbée, J.F.P. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)

Previous studies have shown that overexpression of human apolipoprotein C-I (apoC-I) results in moderate hypercholesterolemia and severe hypertriglyceridemia in mice in the presence and absence of apoE. We assessed whether physiological endogenous apoC-I levels are sufficient to modulate plasma lipid levels independently of effects of apoE on...

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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ApoC-III deficiency prevents hyperlipidemia induced by apoE overexpression

TNO Kwaliteit van Leven (author), Gerritsen, G. (author), Rensen, P.C.N. (author), Kypreos, K.E. (author), Zannis, V.I. (author), Havekes, L.M. (author), van Dijk, K.W. (author)

Adenovirus-mediated overexpression of human apolipoprotein E (apoE) induces hyperlipidemia by stimulating the VLDL-triglyceride (TG) production rate and inhibiting the LPL-mediated VLDL-TG hydrolysis rate. Because apoC-III is a strong inhibitor of TG hydrolysis, we questioned whether Apoc3 deficiency might prevent the hyperlipidemia induced by...

article 2005

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Severe hypertriglyceridemia in human APOC1 transgenic mice is caused by apoC-I-induced inhibition of LPL

TNO Kwaliteit van Leven (author), Berbée, J.F.P. (author), van der Hoogt, C.C. (author), Sundararaman, D. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)

Studies in humans and mice have shown that increased expression of apolipoprotein C-I (apoC-I) results in combined hyperlipidemia with a more pronounced effect on triglycerides (TGs) compared with total cholesterol (TC). The aim of this study was to elucidate the main reason for this effect using human apoC-I-expressing (APOC1) mice. Moderate...

article 2005

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Overexpression of APOC1 in obob mice leads to hepatic steatosis and severe hepatic insulin resistance

Gaubius Instituut TNO (author), Muurling, M. (author), van den Hoek, A.M. (author), Mensink, R.P. (author), Pijl, H. (author), Romijn, J.A. (author), Havekes, L.M. (author), Voshol, P.J. (author)

Obese obob mice with strong overexpression of the human apolipoprotein C1 (APOC1) exhibit excessive free fatty acid (FFA) and triglyceride (TG) levels and severely reduced body weight (due to the absence of subcutaneous adipose tissue) and skin abnormalities. To evaluate the effects of APOC1 overexpression on hepatic and peripheral insulin...

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