Statins prevent oxidized low-density lipoprotein- and lysophosphatidylcholine-induced proliferation of human endothelial cells

• Published in: Vascular pharmacology Vol. 41; no. 2; pp. 67 - 73
• Main Authors: Schaefer, Christian Alexander, Kuhlmann, Christoph Rüdiger Wolfram, Gast, Christine, Weiterer, Sebastian, Li, Fang, Most, Astrid Kerstin, Neumann, Thomas, Backenköhler, Ulrich, Tillmanns, Harald, Waldecker, Bernd, Wiecha, Johannes, Erdogan, Ali
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2004
• Subjects: Cell Division - drug effects; Cell Division - physiology; Cells, Cultured; Dose-Response Relationship, Drug; Endothelial cells; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Growth Inhibitors - pharmacology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Lipoproteins, LDL - antagonists & inhibitors; Lipoproteins, LDL - pharmacology; Lysophosphatidylcholine; Lysophosphatidylcholines - antagonists & inhibitors; Lysophosphatidylcholines - pharmacology; oxLDL; Proliferation; Statin; oxLDL; Statin; Proliferation; Lysophosphatidylcholine; Endothelial cells
• ISSN: 1537-1891; 1879-3649
• DOI: 10.1016/j.vph.2004.05.002

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 μmol/l (cerivastatin), 2.5 μmol/l (simvastatin) and 1 μmol/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 μg/ml) and LPC (20 μmol/l) could be effectively prevented using statins at concentrations between 0.01 and 0.1 μmol/l (cerivastatin), 1 and 2.5 μmol/l (simvastatin) and 0.25 and 1 μmol/l (fluvastatin). This effect of the statins was abolished by preincubation with mevalonate (500 μmol/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.