Effect of statins on lipoprotein receptor expression in cell lines from human mast cells and basophils

Statins are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and widely used to treat hyperlipidaemia. Apart from their direct lipid-lowering effects, statins may also influence lipid metabolism through modulation of low-density lipoprotein (LDL) receptors. Basophils and mast cel...

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Published in:European journal of clinical pharmacology 2003-10, Vol.59 (7), p.507-516
Main Authors: SHUREN LI, DUDCZAK, Robert, VALENT, Peter, KOLLER, Elisabeth, BAGHESTANIAN, Mehrdad, GHANNADAN, Minoo, MINAR, Erich, PIRICH, Christian, ANGELBERGER, Peter, VIRGOLINI, Irene, MEI LI
Format: Article
Language:English
Subjects:
Basophils - drug effects
Basophils - metabolism
Binding Sites
Biological and medical sciences
Cell Line
Dose-Response Relationship, Drug
General and cellular metabolism. Vitamins
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
Mast Cells - drug effects
Mast Cells - metabolism
Medical sciences
Pharmacology. Drug treatments
Radioligand Assay
Receptors, LDL - biosynthesis
Receptors, LDL - metabolism
Thymidine - metabolism
Up-Regulation
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container_issue 7
container_start_page 507
container_title European journal of clinical pharmacology
container_volume 59
creator SHUREN LI
DUDCZAK, Robert
VALENT, Peter
KOLLER, Elisabeth
BAGHESTANIAN, Mehrdad
GHANNADAN, Minoo
MINAR, Erich
PIRICH, Christian
ANGELBERGER, Peter
VIRGOLINI, Irene
MEI LI
description Statins are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and widely used to treat hyperlipidaemia. Apart from their direct lipid-lowering effects, statins may also influence lipid metabolism through modulation of low-density lipoprotein (LDL) receptors. Basophils and mast cells have been reported to express LDL receptors and have been implicated in atherogenesis. The aim of this study was to investigate the effects of statins on the interactions of 125I-LDL with purified primary human blood basophils, a human basophil cell line, KU812, and a human mast cell line, HMC-1. Direct binding experiments were carried out with the primary basophils and KU812 as well as HMC-1 cells before and after pretreatment of the cells with atorvastatin, simvastatin, or cerivastatin. The effects of these three statins on the LDL-uptake and degradation as well as on thymidine incorporation in the cells were also studied. Primary basophils, HMC-1 and KU812 cells expressed two classes of LDL binding sites. Exposure to atorvastatin, simvastatin or cerivastatin increased significantly ( P
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Apart from their direct lipid-lowering effects, statins may also influence lipid metabolism through modulation of low-density lipoprotein (LDL) receptors. Basophils and mast cells have been reported to express LDL receptors and have been implicated in atherogenesis. The aim of this study was to investigate the effects of statins on the interactions of 125I-LDL with purified primary human blood basophils, a human basophil cell line, KU812, and a human mast cell line, HMC-1. Direct binding experiments were carried out with the primary basophils and KU812 as well as HMC-1 cells before and after pretreatment of the cells with atorvastatin, simvastatin, or cerivastatin. The effects of these three statins on the LDL-uptake and degradation as well as on thymidine incorporation in the cells were also studied. Primary basophils, HMC-1 and KU812 cells expressed two classes of LDL binding sites. Exposure to atorvastatin, simvastatin or cerivastatin increased significantly ( P&lt;0.05) the number of 125I-LDL binding sites on primary basophils and HMC-1 as well as KU812 cells. The effects of the statins were dose dependent. The statins also enhanced the uptake and degradation of LDL in primary basophils, HMC-1 and KU812 cells. The increase in the number of LDL binding sites induced by statins was abolished by mevalonic acid (200 micromol/l). Statins had no effect on the thymidine incorporation into the cells in an unstimulated condition. Our results provide evidence for the upregulation of LDL binding sites on human basophils and mast cells by statins. 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Vitamins</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</topic><topic>Mast Cells - drug effects</topic><topic>Mast Cells - metabolism</topic><topic>Medical sciences</topic><topic>Pharmacology. 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ispartof European journal of clinical pharmacology, 2003-10, Vol.59 (7), p.507-516
issn 0031-6970
1432-1041
language eng
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source Springer Link
subjects Basophils - drug effects
Basophils - metabolism
Binding Sites
Biological and medical sciences
Cell Line
Dose-Response Relationship, Drug
General and cellular metabolism. Vitamins
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
Mast Cells - drug effects
Mast Cells - metabolism
Medical sciences
Pharmacology. Drug treatments
Radioligand Assay
Receptors, LDL - biosynthesis
Receptors, LDL - metabolism
Thymidine - metabolism
Up-Regulation
title Effect of statins on lipoprotein receptor expression in cell lines from human mast cells and basophils
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