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Lipidomic approach to evaluate rosuvastatin and atorvastatin at various dosages: Investigating differential effects among statins

Bergheanu, S.C. (author), Reijmers, T. (author), Zwinderman, A.H. (author), Bobeldijk, I. (author), Ramaker, R. (author), Liem, A.-H. (author), van der Greef, J. (author), Hankemeier, T. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)

Objective: Lipid profiling (lipidomics) may be useful in revealing detailed information with regard to the effects on lipid metabolism, the cardiovascular risk and to differentiate between therapies. The aims of the present study were to: (1) analyze in depth the lipid changes induced by rosuvastatin and atorvastatin at different dosages; (2)...

article 2008

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Atorvastatin increases HDL cholesterol by reducing CETP expression in cholesterol-fed APOE*3-Leiden.CETP mice

de Haan, W. (author), van der Hoogt, C.C. (author), Westerterp, M. (author), Hoekstra, M. (author), Dallinga-Thie, G.M. (author), Princen, H.M.G. (author), Romijn, J.A. (author), Jukema, J.W. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)

Objective: In addition to lowering low-density lipoprotein (LDL)-cholesterol, statins modestly increase high-density lipoprotein (HDL)-cholesterol in humans and decrease cholesteryl ester transfer protein (CETP) mass and activity. Our aim was to determine whether the increase in HDL depends on CETP expression. Methods and results: APOE*3-Leiden ...

article 2008

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Mouse models for atherosclerosis and pharmaceutical modifiers

Zadelaar, A.S.M. (author), Kleemann, R. (author), Verschuren, L. (author), de Vries-van der Weij, J. (author), van der Hoorn, J. (author), Princen, H.M. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)

Atherosclerosis is a multifactorial highly-complex disease with numerous etiologies that work synergistically to promote lesion development. The ability to develop preventive and ameliorative treatments will depend on animal models that mimic the human subject metabolically and pathophysiologically and will develop lesions comparable to those in...

article 2007

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Olmesartan and pravastatin additively reduce development of atherosclerosis in APOE*3Leiden transgenic mice

TNO Kwaliteit van Leven (author), van der Hoorn, J.W.A. (author), Kleemann, R. (author), Havekes, L.M. (author), Kooistra, T. (author), Princen, H.M.G. (author), Jukema, J.W. (author)

AIM: This study was designed to investigate the effect of the angiotensin II receptor blocker olmesartan alone, or in combination with standard treatment with a statin, pravastatin, on atherosclerosis development in APOE*3Leiden transgenic mice. METHODS AND RESULTS: Four groups of 15 mice received an atherogenic diet alone (plasma cholesterol 17...

article 2007

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Anti-atherosclerotic effect of amlodipine, alone and in combination with atorvastatin, in APOE*3-Leiden/hCRP transgenic mice

TNO Kwaliteit van Leven (author), Trion, A. (author), Maat, M.de (author), Jukema, W. (author), Maas, A. (author), Offerman, E. (author), Havekes, L. (author), Szalai, A. (author), Laarse, A.V.D. (author), Princen, H. (author), Emeis, J. (author)

We investigated the pleiotropic effects of a calcium antagonist (amlodipine) on early atherosclerosis development in the presence and absence of an HMG-CoA-reductase inhibitor (atorvastatin) in apolipoprotein E*3-Leiden/human C-reactive protein (E3L/CRP) transgenic mice. Male E3L/CRP transgenic mice were fed a cholesterol-containing diet either...

article 2006

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Rosuvastatin reduces plasma lipids by inhibiting VLDL production and enhancing hepatobiliary lipid excretion in ApoE*3-Leiden mice

Delsing, D.J.M. (author), Post, S.M. (author), Groenendijk, M. (author), Solaas, K. (author), van der Boom, H. (author), van Duyvenvoorde, W. (author), de Wit, E.C.M. (author), Bloks, V.W. (author), Kuipers, F. (author), Havekes, L.M. (author), Princen, H.M.G. (author), TNO Kwaliteit van Leven (author)

The present study was designed to investigate the lipid-lowering properties and mechanisms of action of a new HMG-CoA reductase inhibitor, rosuvastatin, in female ApoE*3-Leiden transgenic mice. Mice received a high fat/cholesterol (HFC) diet containing either rosuvastatin (O [control], 0.00125%, 0.0025%, or 0.005% [w/w]) or 0.05% (w/w)...

article 2005

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Evidence for anti-inflammatory activity of statins and PPARα activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro

Kleemann, R. (author), Verschuren, L. (author), de Rooij, B.J. (author), Lindeman, J. (author), de Maat, M.M. (author), Szalai, A.J. (author), Princen, H.M.G. (author), Kooistra, T. (author), Gaubius Instituut TNO (author)

Inflammatory processes, aside from cholesterol, play a central role in atherogenesis. Human C-reactive protein (huCRP) signals systemic inflammation and independently predicts future cardiovascular risk. Cholesterol-lowering statins reduce atherosclerosis and plasma huCRP levels. Evidence is sought for a direct anti-inflammatory statin effect in...

article 2004

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Cardiovascular disease and mortality in statin-treated patients with familial hypercholesterolemia

Mohrschladt, M.F. (author), Westendorp, R.G.J. (author), Gevers Leuven, J.A. (author), Smelt, A.H.M. (author), Gaubius Instituut TNO (author)

Patients with familial hypercholesterolemia (FH) are at an increased risk of premature cardiovascular disease (CVD). The benefits of statin therapy are not well known since no placebo controlled studies have been performed in these patients. The aim of this study was to determine the CVD event and mortality risk in statin-treated patients with...

article 2004

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Differential effects of amlodipine and atorvastatin treatment and their combination on atherosclerosis in ApoE*3-Leiden transgenic mice

Delsing, D.J.M. (author), Jukema, J.W. (author), van de Wiel, M.A. (author), Emeis, J.J. (author), van der Laarse, A. (author), Havekes, L.M. (author), Princen, H.M.G. (author), Gaubius Instituut TNO (author)

This study was designed to investigate the potential antiatherosclerotic effects of the calcium antagonist amlodipine as compared with the HMG-CoA reductase inhibitor atorvastatin and the combination of both in ApoE*3-Leiden transgenic mice. Four groups of 15 ApoE*3-Leiden mice were put on a high-cholesterol diet. One group received 0.002% (wt...

article 2003

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Rosuvastatin reduces atherosclerosis development beyond and independent of its plasma cholesterol-lowering effect in APOE*3-Leiden transgenic mice: Evidence for antiinflammatory effects of rosuvastatin

Kleemann, R. (author), Princen, H.M.G. (author), Emeis, J.J. (author), Jukema, J.W. (author), Fontijn, R.D. (author), Horrevoets, A.J.G. (author), Kooistra, T. (author), Havekes, L.M. (author)

Background - Statins can exert anti-inflammatory antiatherosclerotic effects through an anti-inflammatory action, independent of lowering cholesterol. We addressed the question whether the anti-inflammatory activities of statins can reduce atherosclerosis beyond the reduction achieved by cholesterol lowering per se. Methods and Results - Two...

article 2003

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Raman spectroscopic investigation of atorvastatin, amlodipine, and both on atherosclerotic plaque development in APOE*3 Leiden transgenic mice

Gaubius Instituut TNO (author), van de Poll, S.W.E (author), D.J.M Delsingl, , (author), Jukema, J.Wouter (author), Princen, H.M.G (author), Havekes, L.M. (author), Puppels, G.J. (author), van der Laarse, A. (author)

Raman spectroscopy allows quantitative, non-destructive evaluation of entire, intact atherosclerotic plaques. We quantified the anti-atherosclerotic effects of atorvastatin and amlodipine on progression of atherosclerosis using post-mortem Raman spectroscopic plaque imaging in 28 APOE*3 Leiden transgenic mice who were fed a high fat/high...

article 2002

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C-reactive protein in patients with familial hypercholesterolemia: No effect of simvastatin therapy

Mohrschladt, M.F. (author), de Maat, M.P.M. (author), Westendorp, R.G.J. (author), Smelt, A.H.M (author), Gaubius Instituut TNO (author)

Patients with familial hypercholesterolemia (FH) are especially at risk for premature cardiovascular disease (CVD). Recent studies revealed C-reactive protein (CRP) as a strong predictor of future first or recurrent CVD events, suggesting that CRP plays an important role in the development of atherosclerosis. The aim of this study was to...

article 2001

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Lack of predictability of classical animal models for hypolipidemic activity: A good time for mice?

Krause, B.R. (author), Princen, H.M.G. (author), Gaubius Instituut TNO (author)

Hypolipidemic drugs that are efficacious in man are not always active in classical animal models of dyslipidemia. Inhibitors of HMG-CoA reductase (statins) do not lower plasma cholesterol in rats, but yet this species was alone in providing activity for fibrate-type drugs. Nicotinic acid possesses many desirable features with regard to clinical...

article 1998

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Vastatins have a distinct effect on sterol synthesis and progesterone secretion in human granulosa cells in vitro

van Vliet, A.K. (author), van Thiel, G.C.F. (author), Naaktgeboren, N. (author), Cohen, L.H. (author), Gaubius Instituut TNO (author)

Lovastatin and simvastatin are strong inhibitors of cholesterol synthesis in cultured human granulosa cells, as measured within 6 days after isolation, with IC50-values of respectively 27.0 and 18.2 nM obtained after 3.5 hours of incubation with the drugs. Pravastatin is a much weaker inhibitor of cholesterol synthesis (IC50-value of 977.8 nM)...

article 1996

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Action of lovastatin, simvastatin, and pravastatin on sterol synthesis and their antiproliferative effect in cultured myoblasts from human striated muscle

van Vliet, A.K. (author), Nègre-Arrariou, P. (author), van Thiel, G.C.F. (author), Bolhuis, P.A. (author), Cohen, L.H. (author), TNO Preventie en Gezondheid (author)

Lovastatin, simvastatin, and pravastatin are fairly strong inhibitors of sterol synthesis in human myoblasts in culture. Lovastatin and simvastatin have IC50 values of 19 ± 6 nM and 4.0 ± 2.3 nM, respectively. Pravastatin is a weaker inhibitor of sterol synthesis (IC50 value of 110 ± 38 nM). Through inhibition of mevalonate production, these...

article 1996

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Effects of simvastatin on plasma lipids and apolipoproteins in familial hypercholesterolemic swine

Hasler-Rapacz, J. (author), Kempen, H.J. (author), Princen, H.M.G. (author), Kudchodkar, B.J. (author), Lacko, A. (author), Rapacz, J. (author), Gaubius Instituut TNO (author)

Familial hypercholesterolemia (FHC) in swine, which resembles human familial combined hyperlipidemia, is a complex lipid and lipoprotein disorder associated with the development of severe coronary lesions similar to those occurring in advanced human coronary disease. The disorder is characterized by elevated plasma total cholesterol (TC),...

article 1996

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Different effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on sterol synthesis in various human cell types

van Vliet, A.K. (author), van Thiel, G.C.F. (author), Huisman, R.H. (author), Moshage, H. (author), Yap, S.H. (author), Cohen, L.H. (author), TNO Preventie en Gezondheid (author)

The three vastatins examined, lovastatin, simvastatin and pravastatin, are equally strong inhibitors of the sterol synthesis in human hepatocytes in culture with IC50-values of 4.1, 8.0 and 2.0 nM, respectively. However, in the human extrahepatic cells: umbilical vascular endothelial cells, retinal pigment epithelial cells, cornea fibroblasts...

article 1995

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Cholestrol content of the rat lens is lowered by administration of simvastatin, but not pravastatin

de Vries, A.C.J. (author), Vermeer, M.A. (author), Bredman, J.J. (author), Bar, P.R. (author), Cohen, L.H. (author), Instituut voor verouderings- en vaatziekten onderzoek TNO (author)

The influence of the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors pravastatin and simvastatin on lens cholesterol metabolism was investigated in the rat. Short-term organ culture experiments with explanted lenses from 21-day-old Wistar rats showed that simvastatin was at least 35 times more effective than pravastatin in...

article 1993

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Regulation of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA contents in human hepatoma cell line Hep G2 by distinct classes of mevalonate-derived metabolites

Gaubius instituut TNO (author), Cohen, L.H. (author), Griffioen, M. (author)

Hep G2 cells were incubated under conditions known to influence the HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase activity, e.g. in the presence of compactin (a competitive inhibitor of HMG-CoA reductase itself) and U18666A (a squalene-2,3-epoxide cyclase inhibitor). We studied the effects of these conditions both on the HMG-CoA reductase...

article 1988

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Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in human hepatoma cell line Hep G2. Effects of inhibitors of cholesterol synthesis on enzyme activity

Gaubius instituut TNO (author), Boogaard, A. (author), Griffioen, M. (author), Cohen, L.H. (author)

Incubating Hep G2 cells for 18 h with triparanol, buthiobate and low concentrations (< 0.5 ??M) of U18666A, inhibitors of desmosterol ??24-reductase, of lanosterol 14??-demethylase and of squalene-2,3-epoxide cyclase (EC 5.4.99.7) respectively, resulted in a decrease of the HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase activity....

article 1987