Effect of simvastatin in familial hypercholesterolemia on the affinity of electronegative low-density lipoprotein subfractions to the low-density lipoprotein receptor

Benı́tez, Sònia; Ordóñez-Llanos, Jordi; Franco, M.; Marı́n, Carmen; Paz, Elier; López‐Miranda, José; Otal, Carles; Pérez‐Jiménez, Francisco; Sánchez-Quesada, José Luís

doi:10.1016/j.amjcard.2003.10.034

Cited by 44 publications

(36 citation statements)

References 28 publications

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“…These results suggest that statins can lower apoB-100 levels by decreasing PR and increasing FCR, with somewhat variable effects that may depend on the patient population and statin regimen. In the present study, we found that simvastatin decreased the pool sizes of VLDL and LDL apoB-100 by increasing the apoB-100 FCRs in these fractions, an effect most likely mediated by the activation of the expression of the LDL receptor (47) and, alternatively, by statin-induced changes in the composition of apoB-containing lipoproteins increasing their affinity for the LDL receptor (48). Compared with monotherapies, the combination of ezetimibe and simvastatin incrementally enhances the catabolism of VLDL and LDL apoB-100 with no significant effect on VLDL and LDL apoB-100 PR.…”

Section: Discussionmentioning

confidence: 51%

Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia

Tremblay

Lamarche

Hogue

et al. 2009

Journal of Lipid Research

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Sixteen hyperlipidemic men were enrolled in a randomized, placebo-controlled, double-blind, cross-over study to evaluate the effect of ezetimibe 10 mg and simvastatin 40 mg, coadministered and alone, on the in vivo kinetics of apolipoprotein (apo) B-48 and B-100 in humans. Subjects underwent a primed-constant infusion of a stable isotope in the fed state. The coadministration of simvastatin and ezetimibe significantly reduced plasma concentrations of cholesterol (243.0%), LDL-C (253.6%), and triglycerides (244.0%). Triglyceride-rich lipoproteins (TRL) apoB-48 pool size (PS) was significantly decreased (248.9%) following combination therapy mainly through a significant reduction in TRL apoB-48 production rate (PR) (238.0%). The fractional catabolic rate (FCR) of VLDL and LDL apoB-100 were significantly increased with all treatment modalities compared with placebo, leading to a significant reduction in the PS of these fractions. We also observed a positive correlation between changes in TRL apoB-48 PS and changes in TRL apoB-48 PR (r 5 0.85; P , 0.0001) with combination therapy. Our results indicate that treatment with simvastatin plus ezetimibe is effective in reducing plasma TRL apoB-48 levels and that this effect is most likely mediated by a reduction in the intestinal secretion of TRL apoB-48. Our study also indicated that the reduction in LDL-C concentration following combination therapy is mainly driven by an increase in FCR of apoB-100 containing lipoproteins.-Tremblay, A. J., B. Lamarche, J-C. Hogue, and P. Couture. Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia. J. Lipid Res.

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Section: Discussionmentioning

confidence: 51%

Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia

Tremblay

Lamarche

Hogue

et al. 2009

Journal of Lipid Research

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“…This outcome is likely mediated by the inhibitory effect of atorvastatin on cholesterol synthesis and the ensuing activation of the cholesterol-sensing transcription factor sterol-regulatory element binding protein, which then mediates the activation of the expression of the LDL receptor, one of its target genes (24). Alternatively, atorvastatin may also induce changes in the composition of the apoB-containing lipoproteins and thus increase their affinity for the LDL receptor (25). In addition, atorvastatin has been shown to increase the expression and activity of lipoprotein lipase (26), thus favoring rapid lipolysis of lipoproteins.…”

Section: Discussionmentioning

confidence: 99%

Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism

Lamon‐Fava

Diffenderfer

Barrett

et al. 2007

Journal of Lipid Research

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Nine hypercholesterolemic and hypertriglyceridemic subjects were enrolled in a randomized, placebocontrolled, double-blind, crossover study to test the effect of atorvastatin 20 mg/day and 80 mg/day on the kinetics of apolipoprotein B-100 (apoB-100) in triglyceride-rich lipoprotein (TRL), intermediate density lipoprotein (IDL), and LDL, of apoB-48 in TRL, and of apoA-I in HDL. Compared with placebo, atorvastatin 20 mg/day was associated with significant reductions in TRL, IDL, and LDL apoB-100 pool size as a result of significant increases in fractional catabolic rate (FCR) without changes in production rate (PR). Compared with the 20 mg/day dose, atorvastatin 80 mg/day caused a further significant reduction in the LDL apoB-100 pool size as a result of a further increase in FCR. ApoB-48 pool size was reduced significantly by both atorvastatin doses, and this reduction was associated with nonsignificant increases in FCR. The lathosterol-campesterol ratio was decreased by atorvastatin treatment, and changes in this ratio were inversely correlated with changes in TRL apoB-100 and apoB-48 PR. No significant effect on apoA-I kinetics was observed at either dose of atorvastatin. Our data indicate that atorvastatin reduces apoB-100-and apoB-48-containing lipoproteins by increasing their catabolism and has a dose-dependent effect on LDL apoB-100 kinetics. Atorvastatin-mediated changes in cholesterol homeostasis may contribute to apoB PR regulation.-Lamon-Fava, S.,

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“…Martino et al (12) showed that already in children oxidative stress may have an important role in the occurrence of premature atherosclerosis. In this context, electronegative low-density lipoprotein [LDL (2)] has been widely monitored in adults and now it is considered a potential biomarker associated with initiation and progression of atherosclerosis (13)(14)(15)(16). Despite these observations, a limited number of studies have detected LDL (2) in children and adolescents (17,18).…”

mentioning

confidence: 99%

Is Plasma Alpha-Tocopherol Associated with Electronegative LDL in Obese Adolescents?

Silva

Mello

Sanches

et al. 2013

J Nutr Sci Vitaminol

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Summary Obesity has increased in children and adolescents. What is reflected in the early occurrence of cardiometabolic alterations, like hypertension and type 2 diabetes, where the oxLDL formation is stimulated. Various studies have shown that plasma a-tocopherol (a-TP) can protect LDL against oxidation. Nevertheless, the action of plasma a-TP in cardiovascular diseases remains controversial. We conducted a cross-sectional study to evaluate plasma a-TP and its impact on the concentration of LDL(2). Adolescents (n5150) of both sexes were classified into three groups: healthy weight (HW; 50%), overweight (OV; 22%), and obese (OB; 28%). Lipid profile, LDL(2), anti-oxLDL and anti-LDL(2) antibodies, CRP (ELISA) and plasma a-TP (HPLC) were analyzed. Demographic, anthropometric, and food intake data were evaluated. Crude and energy-adjusted intake of vitamin E in the OB group were higher than in the HW group (p,0.001). Crude and energy-adjusted vitamin E intakes were not correlated with plasma a-TP (r520.07; p50. 412 and r520.064; p50.467, respectively). Subjects in the OB group had higher TC and LDL-C and lower HDL-C than in the HW and OV groups. C-reactive protein and anti-oxLDL antibodies changed as a function of BMI. The impact of obesity was reinforced by high values for LDL(2) and low content of plasma a-TP in comparison with the HW (p,0.001) and OV groups (p50.03). This negative profile was maintained for the ratio between a-TP and TC or LDL-C. Plasma a-TP, a-TP/TC and a-TP/LDL-C were negatively associated with LDL(2) and other cardiometabolic risk factors (BMI, WC, AC and anti-oxLDL). Our results demonstrate that obesity in adolescents is associated with high levels of LDL(2) and low plasma a-TP content.

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Effect of simvastatin in familial hypercholesterolemia on the affinity of electronegative low-density lipoprotein subfractions to the low-density lipoprotein receptor

Cited by 44 publications

References 28 publications

Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia

Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia

Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism

Is Plasma Alpha-Tocopherol Associated with Electronegative LDL in Obese Adolescents?

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