title: Statins prevent oxidized low-density lipoprotein- and lysophosphatidylcholine-induced proliferation of human endothelial cells.
abstract: The proliferation of endothelial cells is induced by oxidized low-density lipoprotein (oxLDL) and its major component, lysophosphatidylcholine (LPC). The aim of this study was to investigate the effect of statins on the proliferation of endothelial cells derived from human umbilical cord veins (HUVEC). Cerivastatin, simvastatin and fluvastatin caused a dose-dependent inhibition of endothelial cell growth (n=12; P<.01) when using cell counts and [3H]-thymidine incorporation, respectively. The strongest inhibition of HUVEC proliferation was achieved at statin concentrations of 0.1 micromol/l (cerivastatin), 2.5 micromol/l (simvastatin) and 1 micromol/l (fluvastatin). Cell counts were significantly reduced from 22937+/-280.6 (control) to 7791+/-133.6 (cerivastatin), 7292+/-146.6 (simvastatin) and 6792+/-135.5 (fluvastatin) (n=12; P<.01). Interestingly, cell proliferation induced by oxLDL (10 microg/ml) and LPC (20 micromol/l) could be effectively prevented using statins at concentrations between 0.01 and 0.1 micromol/l (cerivastatin), 1 and 2.5 micromol/l (simvastatin) and 0.25 and 1 micromol/l (fluvastatin). This effect of the statins was abolished by preincubation with mevalonate (500 micromol/l). Our results demonstrate an interesting direct effect of statins on the proliferation of human endothelial cells induced by oxLDL and LPC, which may be beneficial to prevent vascular effects of these atherogenic lipids.
authors.affiliation: Department of Cardiology and Angiology, Justus-Liebig University of Giessen, Klinikstr. 36, 35 392 Giessen, Germany.
authors.forename: Christian Alexander
authors.initials: CA
authors.lastname: Schaefer
authors.forename: Christoph Rüdiger Wolfram
authors.initials: CR
authors.lastname: Kuhlmann
authors.forename: Christine
authors.initials: C
authors.lastname: Gast
authors.forename: Sebastian
authors.initials: S
authors.lastname: Weiterer
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Astrid Kerstin
authors.initials: AK
authors.lastname: Most
authors.forename: Thomas
authors.initials: T
authors.lastname: Neumann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Backenköhler
authors.forename: Harald
authors.initials: H
authors.lastname: Tillmanns
authors.forename: Bernd
authors.initials: B
authors.lastname: Waldecker
authors.forename: Johannes
authors.initials: J
authors.lastname: Wiecha
authors.forename: Ali
authors.initials: A
authors.lastname: Erdogan
mesh_terms: D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D006131:Growth Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; C099252:oxidized low density lipoprotein