The effects of simvastatin on plasma lipoproteins and cholesterol homeostasis in patients with heterozygous familial hypercholesterolaemia

Hagemenas, F. C.; Pappu, Anuradha S.; Illingworth, D. Roger

doi:10.1111/j.1365-2362.1990.tb02262.x

Cited by 40 publications

(15 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, 44 W anner/Lubrich-Birkner/Summ/W leland/ Simvastatin in CAPD Patients Schollmeyer this group of patients, theoretically prone to muscular dam age and side effects, were monitored closely in the present study to detect complications early. Hagemenas et al [30] showed that 100 mg of M C simvastatin given in a single dose to healthy subjects was completely cleared from the circula tion after 12 h. Comparable results were obtained in our patients since no inhibitory activity of simvastatin could be detected in plasma 12 h after simvastatin administration. This would confirm the lack of clinical side effects and laboratory abnormalities.…”

Section: Discussionsupporting

confidence: 68%

Effect of Simvastatin on Qualitative and Quantitative Changes of Lipoprotein Metabolism in CAPD Patients

Wanner

Lubrich-Birkner

Summ

et al. 1992

Nephron

View full text Add to dashboard Cite

The efficacy of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, was investigated in 12 patients treated with continuous ambulatory peritoneal dialysis (CAPD), displaying hypercholesterolemia and moderate hypertriglyceridemia. After a 4-week placebo period, simvastatin was administered in increasing doses over a period of 3 months (1^st month 10 mg; 2^nd month 20 mg and 3rd month 40 mg day^-1). Simvastatin reduced total serum cholesterol (300.0 + 15.5 vs. 193.0 ± 8.0; -35%), LDL cholesterol (203.8 ± 13.0 vs. 104.7 ± 6.0; -48.0%) as well as apolipoprotein B (132.3 ± 6.6 vs. 77.8 ± 2.7 mg/dl; -40%). Furthermore, the ratio of LDL apo B/LDL cholesterol increased significantly (0.55 ± 0.016 vs. 0.64 ± 0.027). Another remarkable effect was the reduction of cholesterol concentration in VLDL (47.8 ± 5.6 vs. 30.4 ± 5.2; -35%). Therefore, the ratio of triglycerides/cholesterol in VLDL increased (3.57 ± 0.3 vs. 4.28 ± 0.29), indicating VLDL formation poor in cholesterol and rich in triglycerides. However, HDL cholesterol increased significantly from 48.6 ± 4.4 to 57.9 ± 5.3 mg/dl (23%). Lipoprotein(a) levels were increased as compared to controls (420 ± 73 vs. 145 ± 26 U/l), but were not influenced significantly by simvastatin treatment (539 ± 99 U/l, 3rd month). No evidence for notable clinical side effects and laboratory abnormalities were reported. Measurement of simvastatin plasma levels 12 h after drug administration (single dose 40 mg) showed no detectable plasma values. At present, it appears that CAPD patients with high serum cholesterol are good candidates for the treatment with HMG-CoA reductase inhibitors.

show abstract

Section: Discussionsupporting

confidence: 68%

Effect of Simvastatin on Qualitative and Quantitative Changes of Lipoprotein Metabolism in CAPD Patients

Wanner

Lubrich-Birkner

Summ

et al. 1992

Nephron

View full text Add to dashboard Cite

show abstract

“…It has also been observed that statins up-regulate hepatic LDLR expression and inhibition of HMG-CoA reductase results in a secondary increase in LDLR activity (3,24,25). Therefore, it is possible that statin therapy might affect the results even though peripheral lymphocytes, and not hepatocytes, were used in this study (26,27). There have been some conflicting reports about the relationship between statin therapy and LDLR activity of lymphocytes (12).…”

Section: Discussionmentioning

confidence: 97%

A novel method for determining functional LDL receptor activity in familial hypercholesterolemia: Application of the CD3/CD28 assay in lymphocytes

Tada

Kawashiri

Noguchi

et al. 2009

Clinica Chimica Acta

View full text Add to dashboard Cite

Abbreviated title: An improved assay for LDL receptor activity using anti-CD3/CD28 beads Abbreviations: DiI, 3,3"--dioctadecylindocarbocyanin; FH, familial hypercholesterolemia; NARC-1, neural apoptosis-regulated convertase 1; FITC, fluorescein isothiocyanate; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LDLR, low-density lipoprotein receptor; LPDS, lipoprotein deficient serum; rIL-2, recombinant interleukin-2; MF, mean fluorescence; TC, total cholesterol; CV, coefficient of variation. 3 AbstractBackground: The objective of this study was to develop a new and simple method for measuring low-density lipoprotein receptor (LDLR) activity using peripheral lymphocytes enabling us to clinically diagnose familial hypercholesterolemia (FH) and ascertain the involved mutations (such as K790X mutation), that might not be clearly detected in the conventional method.Methods: Our method comprised the following 2 features: First, we used anti-CD3/CD28 beads to stimulate T-lymphocytes to obtain a uniform fraction of lymphocytes and maximum up-regulation of LDLR. Second, we excluded the possibility of overestimation of lymphocyte signals bound only to its surface, by adding heparin to the cultured lymphocytes used for the LDLR assay.Results: Based on the genetic mutation, the FH subjects were divided into two groups, K790X, (n = 20) and P664L, (n = 5), and their LDLR activities was measured by this method, which was found to be 55.3 ± 8.9% and 63.9 ± 13.8%, respectively, of that of the control group (n = 15). In comparison, the LDLR activity was 86.1 ± 11.6% (K790X) and 73.3 ± 6.3% (P664L) of that of the control group when measured by the conventional method, indicating that impairment of LDLR function in FH K790X subjects was much more clearly differenciated with our method than with the conventional method (paired t-test, p < 0.0001). The levels of LDLR expression also showed similar tendencies, that is, 89.4 ± 13.2% (K790X) and 76.9 ± 17.4% (P664L) of that of the control group when measured by the conventional method, and 78.1 ± 9.7% (K790X) and 70.3 ± 26.5% (P664L) when measured by our new method. In addition, we confirmed that there was little influence of statin treatment on LDLR activity among the study subjects when our method was used.Conclusion: These results demonstrate that our new method is applicable for measuring LDLR 4 activity, even in subjects with an internally defective allele, and that T-lymphocytes of the FH K790X mutation possess characteristics of that allele.

show abstract

“…The hypocholesterolemic effect of lovastatin administered against the background of obsidan depends on its diurnal dose. There are diverse published data on the effect of lovastatin on the rate of Ch synthesis in peripheral blood lymphocytes [7,8,13]. We showed that this effect depends on the diurnal dose of the preparation and on the degree of the drop of total serum Ch.…”

Section: Methodsmentioning

confidence: 79%

“…These results indicate the existence of an inverse relationship between the rate of Ch synthesis in lymphocytes and the level of serum Ch. The synthesis of Ch in lymphocytes depends on the concentration of Ch in the cell, i.e., it is regulated by feedback [5,8]. The elevation of the total Ch level observed after 6 months of lovastatin treatment was accompanied by a decreased rate of Ch synthesis in the lymphocytes.…”

Section: Methodsmentioning

confidence: 99%

Peculiarities of changes in the rate of cholesterol synthesis in lymphocytes and lipid and lipoprotein peripheral blood levels in patients with ischemic heart disease and hypercholesterolemia in the course of combined treatment with lovastatin and obsidan

et al. 1994

View full text Add to dashboard Cite

It is shown that the level of total serum cholesterol dropped and the rate of cholesterol synthesis in lymphocytes remained unchanged after 12 months of lovastatin treatment (20 rag/day) in patients with coronary heart disease. The administration of lovastatin abolished the deleterious effect of obsidan on the blood lipid spectrum. Key Words: lymphocytes; cholesterol synthesis; lovastatin; hypercholesterolemiaPeripheral blood lymphocytes represent a convenient model for the investigation of the intensity of cholesterol (Ch) synthesis in patients with various dyslipidemias [10,14]. Competitive inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCoA-reductase), a rate-limiting enzyme of cholesterol synthesis, are used for the correction of hypercholesterolemia [10,11]. Among them lovastatin is the most widely used and its hypocholesterolemic effect has been studied at length [6,10,11]. It is attributed to an activation of B,E-receptors and accelerated catabolism of low-density lipoproteins (LDL) [13]. ~-Adrenoblockers are commonly used for the management of coronary heart disease (CHD). However, they have been shown to affect the level of serum lipids and other parameters determining the development of the atherosclerotic process and CHD [1,15]. The objective of the present study was to evaluate the effect of different doses of lovastatin on the rate of cholesterol synthesis in lymphocytes and to investigate the dynamics of levels of serum lipids, lipoproteins, and A1 and B apolipoproteins in the serum of hypercholesterolemic patients treated with obsidan. MATERIALS AND METHODSThe material for the study consisted of serum and freshly isolated peripheral blood lymphocytes from CHD patients with angiographlcaUy verified atherosclerosis of the coronary arteries. In all, 37 male patients 40-60 years old with a level of total cholesterol higher than 250 mg/dl were examined. The therapeutic scheme is presented in Fig. 1. All patients were following the guidelines for hypolipi-

show abstract

The effects of simvastatin on plasma lipoproteins and cholesterol homeostasis in patients with heterozygous familial hypercholesterolaemia

Cited by 40 publications

References 28 publications

Effect of Simvastatin on Qualitative and Quantitative Changes of Lipoprotein Metabolism in CAPD Patients

Effect of Simvastatin on Qualitative and Quantitative Changes of Lipoprotein Metabolism in CAPD Patients

A novel method for determining functional LDL receptor activity in familial hypercholesterolemia: Application of the CD3/CD28 assay in lymphocytes

Peculiarities of changes in the rate of cholesterol synthesis in lymphocytes and lipid and lipoprotein peripheral blood levels in patients with ischemic heart disease and hypercholesterolemia in the course of combined treatment with lovastatin and obsidan

Contact Info

Product

Resources

About