Statins prevent oxidized low-density lipoprotein- and lysophosphatidylcholine-induced proliferation of human endothelial cells.
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.
Schaefer
Christian Alexander
CA
Department of Cardiology and Angiology, Justus-Liebig University of Giessen, Klinikstr. 36, 35 392 Giessen, Germany.
Kuhlmann
Christoph Rüdiger Wolfram
CR
Gast
Christine
C
Weiterer
Sebastian
S
Li
Fang
F
Most
Astrid Kerstin
AK
Neumann
Thomas
T
Backenköhler
Ulrich
U
Tillmanns
Harald
H
Waldecker
Bernd
B
Wiecha
Johannes
J
Erdogan
Ali
A
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*
D006131:Growth Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; C099252:oxidized low density lipoprotein