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Henneman, P. (author), van der Sman-de Beer, F. (author), Moghaddam, P.H. (author), Huijts, P. (author), Stalenhoef, A.F.H. (author), Kastelein, J.J.P. (author), van Duijn, C.M. (author), Havekes, L.M. (author), Frants, R.R. (author), van Dijk, K.W. (author), Smelt, A.H.M. (author), TNO Kwaliteit van Leven (author)Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In...article 2009
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Henneman, P. (author), Schaap, F.G. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), Frants, R.R. (author), van Tol, A. (author), Hattori, H. (author), Smelt, A.H.M. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)Objective: The recently discovered apoAV is hypothesized to affect triglyceride metabolism by stimulating the lipolysis of triglycerides in VLDL and chylomicrons. We set out to determine the association between increased serum TG levels, plasma apoAV levels, and polymorphism of the APOA5 gene, with specific emphasis on the APOA5 S19W variation....article 2007
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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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Hofman, M.K. (author), Groenendijk, M. (author), Verkuijlen, P.J.J.H. (author), Jonkers, I.J.A.M. (author), Mohrschladt, M.F. (author), Smelt, A.H.M. (author), Princen, H.M.G. (author), Gaubius Instituut TNO (author)The rate-limiting enzyme in the conversion of cholesterol into bile acids is cholesterol 7alpha-hydroxylase (CYP7A1). An A to C substitution 278 bp upstream in the promoter of the CYP7A1 gene was found to be associated with variations in serum lipid levels in normolipidaemic populations. In the present study, we investigated the involvement of...article 2004
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de Beer, F. (author), Stalenhoef, A.F.H. (author), Hoogerbrugge, N. (author), Kastelein, J.J.P. (author), Leuven, J.A.G. (author), van Duijn, C.M. (author), Havekes, L.M. (author), Smelt, A.H.M. (author), Gaubius Instituut TNO (author)Type III hyperlipoproteinemia (HLP) is mainly found in homozygous carriers of apolipoprotein E2 (apoE2, Arg158→Cys). Only a small percentage (<5%) of these apoE2 homozygotes develops hyperlipidemia, indicating that additional environmental and genetic factors contribute to the expression of type III HLP. In the present study, first, the...article 2002
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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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de Beer, F. (author), van Dijk, K.W. (author), Jong, M.C. (author), van Vark, L.C. (author), van der Zee, A. (author), Hofker, M.H. (author), Fallaux, F.J. (author), Hoeben, R.C. (author), Smelt, A.H.M. (author), Havekes, L.M. (author), Gaubius Instituut TNO (author)The apolipoprotein E2 (Lys146→Gln) variant is associated with a dominant form of familial dysbetalipoproteinemia. Heterozygous carriers of this variant have elevated levels of plasma triglycerides, cholesterol, and apolipoprotein E (apoE). It was hypothesized that the high amounts of triglycerides in the very low density lipoprotein (VLDL)...article 2000
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TNO Preventie en Gezondheid (author), Sijbrands, E.J.G. (author), Westendorp, R.G.J. (author), Paola Lombardi, M. (author), Havekes, L.M. (author), Frants, R.R. (author), Kastelein, J.J.P. (author), Smelt, A.H.M. (author)Life expectancy of patients with familial hypercholesterolaemia is decreased. Some untreated patients reach a normal life span and, therefore, additional risk factors and the type of mutation in the low-density lipoprotein (LDL) receptor gene are likely to influence the clinical outcome. We determined all cause mortality in kindreds with the...article 2000
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TNO Preventie en Gezondheid (author), de Man, F.H.A.F. (author), Jonkers, I.J.A.M. (author), Schwedhelm, E. (author), Smelt, A.H.M. (author), Onkenhout, W. (author), van Duyvenvoorde, W. (author), Buytenhek, R. (author), Leuven, J.A.G. (author), Troost, R. (author), van der Laarse, A. (author), Princen, H.M.G. (author)Although there is evidence that hyperlipidemia and predominance of small dense low density lipoproteins (LDLs) are associated with increased oxidative stress, the oxidation status in patients with hypertriglyceridemia (HTG) has not been studied in detail. Therefore, we studied urinary levels of F2-isoprostanes (8-isoprostaglandin F(2α) and 2,3...article 2000
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de Beer, F. (author), Hendriks, W.L. (author), van Vark, L.C. (author), Kamerling, S.W.A. (author), van Dijk, K.W. (author), Hofker, M.H. (author), Smelt, A.H.M. (author), Havekes, L.M. (author), Gaubius instituut TNO (author)The binding of β-VLDL to heparan sulfate proteoglycans (HSPG) has been reported to be stimulated by both apoE and lipoprotein lipase (LPL). In the present study we investigated the effect of the isoform and the amount of apoE per particle, as well as the role of LPL on the binding of β-VLDL to HSPG. Therefore, we isolated β-VLDL from transgenic...article 1999
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Sijbrands, E.J.G. (author), Hoffer, M.J.V. (author), Meinders, A.E. (author), Havekes, L.M. (author), Frants, R.R. (author), Smelt, A.H.M. (author), de Knijff, P. (author), Gaubius instituut TNO (author)More than 90% of patients with type III hyperlipoproteinemia are homozygous carriers of the apolipoprotein (apo) E*2 allele. The great majority of these apoE2(Arg158→Cys) homozygotes in the general population, however, are normolipidemic. Apparently, expression of the hyperlipidemic state requires additional genetic and/or environmental factors,...article 1999
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Sijbrands, E.J.G. (author), Lombardi, M.P. (author), Westendorp, R.G.J. (author), Gevers Leuven, J.A. (author), Meinders, A.E. (author), van der Laarse, A. (author), Frants, R.R. (author), Havekes, L.M. (author), Smelt, A.H.M. (author), Gaubius Instituut TNO (author)In patients heterozygous for familial hypercholesterolemia, the low- density lipoprotein (LDL) cholesterol lowering effect of β-hydroxy-β- methylglutaryl coenzyme A reductase inhibitors may depend on the nature of the mutation in the LDL receptor gene. To test this hypothesis, we compared the response to simvastatin, 20 mg daily for 9 weeks,...article 1998
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de Man, F.H.A.F. (author), de Beer, F. (author), van der Laarse, A. (author), Smelt, A.H.M. (author), Leuven, J.A.G. (author), Havekes, L.M. (author), Gaubius Instituut TNO (author)Lipoprotein lipase (LPL) is bound to heparan sulphate proteoglycans (HSPG) at the luminal surface of endothelium. It is the key enzyme involved in the hydrolysis of very low density lipoproteins (VLDL). Prior to lipolysis by LPL, the lipoproteins are considered to interact with vessel wall HSPG. Apolipoprotein (apo) E is thought to mediate this...article 1998
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Gaubius Instituut TNO (author), de Man, F.H.A.F. (author), de Beer, F. (author), van der Laarse, A. (author), Smelt, A.H.M. (author), Havekes, L.M. (author)An in vitro assay to study lipolysis of very low density lipoproteins (VLDL) by heparan sulfate proteoglycan (HSPG-bound lipoprotein lipase (LPL) was developed. Optimal conditions for VLDL lipolysis by HSPG-bound LPL were obtained by incubating plastic wells with 0.5 ug HSPG and 1.5 ug LPL, subsequently. Control experiments with heparinase...article 1997
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Sijbrands, E.J.G. (author), Westendorp, R.G.J. (author), Hoffer, M.J.V. (author), Frants, R.R. (author), Meinders, A.E. (author), Souverijn, J.H.M. (author), Leuven, J.A.G. (author), van der Laarse, A. (author), Havekes, L.M. (author), Smelt, A.H.M. (author), Gaubius Instituut TNO (author)Apolipoprotein (ape) E2 and high insulin levels are associated with the severity of hypertriglyceridemia in patients with combined hyperlipidemia. To study how these determinants affect very low-density lipoprotein (VLDL) in combined hyperlipidemic patients, we characterized VLDL particles in 106 unrelated patients with combined hyperlipidemia....article 1996
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Hau, M.-F. (author), Smelt, A.H.M. (author), Bindels, A.J.G.H. (author), Sijbrands, E.J.G. (author), van der Laarse, A. (author), Onkenhout, W. (author), van Duyvenvoorde, W. (author), Princen, H.M.G. (author), Gaubius Instituut TNO (author)In hypertriglyceridemic (HTG) patients the addition of fish oil to the diet causes a marked reduction in the concentration of triglyceride-rich lipoproteins in the serum. To investigate the effects of fish oil on the oxidation resistance of VLDL and LDL in HTG patients, nine male patients received 1 g/d fish oil (containing 55.7% n-3...article 1996
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Gaubius Instituut TNO (author), Lombardi, P. (author), Sijbrands, E.J.G. (author), van de Giessen, K. (author), Smelt, A.H.M. (author), Kastelein, J.J.P. (author), Frants, R.R. (author), Havekes, L.M. (author)Familial hypercholesterolemia (FH) results from mutations in the low density lipoprotein receptor (LDLR) gene. We applied denaturing gradient gel electrophoresis (DGGE) to screen for sequence variations in the coding and splice site consensus sequences of the LDLR gene. For amplification of each exon by the polymerase chain reaction (PCR),...article 1995
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Zhao, S.P. (author), Bastiaanse, E.M.L. (author), Hau, M.F. (author), Smelt, A.H.M. (author), Gevers Leuven, J.A. (author), van der Laarse, A. (author), van 't Hooft, F.M. (author), TNO Preventie en Gezondheid (author)To assess the presence and composition of very-low-density lipoprotein (VLDL) in various types of hyperlipoproteinemia, a method of density gradient ultracentrifugation has been developed. After 2 hours of density gradient ultracentrifugation, human serum VLDL is separated into two distinct VLDL cholesterol peaks (VLDL1 and VLDL2). The two VLDL...article 1994
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- Wijsman, B.P. (author), Adrichem, C.M. (author), van 't Hooft, F.M. (author), Gevers Leuven, J.A. (author), van der Laarse, A. (author), Smelt, A.H.M. (author), Gaubius instituut Instituut voor verouderings- en vaatziekten onderzoek TNO (author) article 1993
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Meijer, J. (author), Smelt, A.H.M. (author), van 't Hooft, F.M. (author), Gevers Leuven, J.A. (author), Zwetsloot-Schonk, J.H.M. (author), van den Berg, J.M.J. (author), Gaubius Instituut TNO (author)Een lipiden polikliniek houdt zich bezig met de behandeling van patiënten met een verhoofd cholesterolgehalte (hypercholesterolemie) in het bloed. Verschillende vormen van hypercholesterolemie kunnen op basis van bloedparameters worden onderscheiden, o.a. volgens de classificatie van Fredrickson. Deze classificatie kan automatisch worden...conference paper 1990