title: The effects of different types of statins on proliferation and migration of HGF-induced Human Umbilical Vein Endothelial Cells (HUVECs).
abstract: OBJECTIVE
  Statins are HMG-CoA reductase inhibitors within the framework of cholesterol biosynthesis and used to lower the low-density lipoprotein (LDL). There are other aspects of statins can deploy a protective effect, even without the LDL's lowering. The aim of this study is to investigate the effects of different type of statins on proliferative and migrative behaviors of Hepatocyte Growth Factor (HGF) induced human umbilical vein endothelial cells (HUVECs).
  
  
  METHODS
  Human umbilical vein endothelial cells were isolated and cultured. Groups were designed in order to observe the effects of every individual substance. HUVECs were stimulated with HGF, statins and farnesylpyrophosphat ammonium salt (FPP) or geranylgeranyl-pyrophosphate (GGPP), respectively. Cell proliferations were counted 48 hours after initial stimuli and distances between migration fronts were used in migration analyses.
  
  
  RESULTS
  All types of statins showed significant anti-migrative and anti-proliferative characters. Simvastatin and fluvastatin but not cerivastatin, were able to inhibit the HGF-depending migration and showed a significant effect on the inhibition of the isoprenylation (GGPP). Only simvastatin influenced the HGF-depending migration via inhibiting the isoprenylation process through GGPP. Cerivastatin significantly decreased the proliferation and Fluvastatin significantly enhanced the migration behaviors of HUVECs when they were co-incubated with methyl-8-cyclodextrin (MCD).
  
  
  CONCLUSIONS
  Statins countermand the proproliferative and as well as the promigrative effect of HGF on HUVECs. The mechanisms which provoke this effect are dependent on the type of statin. Direct interactions of statins with lipid rafts play a significant role in the endothelial cell mechanisms.
authors.affiliation: Department of Internal Medicine, Wuppertal Research and Medical Center, Angiology Wuppertal, Germany. burgazlk@uni-koeln.de.
authors.forename: K M
authors.initials: KM
authors.lastname: Burgazli
authors.forename: K L
authors.initials: KL
authors.lastname: Bui
authors.forename: M
authors.initials: M
authors.lastname: Mericliler
authors.forename: A T
authors.initials: AT
authors.lastname: Albayrak
authors.forename: M
authors.initials: M
authors.lastname: Parahuleva
authors.forename: A
authors.initials: A
authors.lastname: Erdogan
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology; D019821:Simvastatin / Q000494:pharmacology; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011106:Polyisoprenyl Phosphates; D011725:Pyridines; D012717:Sesquiterpenes; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D000077340:Fluvastatin; D017228:Hepatocyte Growth Factor; C004808:farnesyl pyrophosphate; D019821:Simvastatin; C086276:cerivastatin; C002963:geranylgeranyl pyrophosphate