title: Effect of lovastatin on coxsackievirus B3 infection in human endothelial cells.
abstract: OBJECTIVE
  The coxsackie and adenovirus receptor (CAR) mediates the entry of coxsackievirus B (CVB) and adenovirus into host cells and is, therefore, a key determinant for the molecular pathogenesis of viral diseases such as myocarditis. The aim was to investigate the influence of HMG-CoA reductase inhibitor lovastatin on CAR expression in endothelial cells.
  
  
  METHODS
  Human umbilical vein endothelial cells (HUVECs) were exposed to different concentrations of lovastatin (0.05-5 μmol/l) for up to 48 h. Alterations in CAR expression were examined by quantitative real-time PCR (qRT-PCR) and flow cytometry. In addition, after treatment with 1 μmol/l lovastatin for 48 h, HUVECs were infected for 8 h with CVB3 and virus replication was detected by qRT-PCR using viral-specific TaqMan probes.
  
  
  RESULTS
  We found that lovastatin decreases CAR mRNA expression by up to 80% (p < 0.01) and CAR protein expression by up to 19% (p < 0.01), in a concentration-dependent manner. Moreover, virus replication of CVB3 was significantly inhibited after lovastatin treatment (p < 0.05). The signaling mechanism of CAR down-regulation by lovastatin depends on the Rac1/Cdc42 pathway.
  
  
  CONCLUSIONS
  This study shows for the first time that lovastatin reduces the expression of CAR and subsequently the replication of CVB3 in HUVECs.
authors: Department of Cardiology, Heart and Diabetes Center NRW, Ruhr University of Bochum, Georgstr. 11, 32545, Bad Oeynhausen, NRW, Germany, bwerner@hdz-nrw.de.
authors: Bianca
authors: B
authors: Werner
authors: Sven
authors: S
authors: Dittmann
authors: Carsten
authors: C
authors: Funke
authors: Klaus
authors: K
authors: Überla
authors: Cornelia
authors: C
authors: Piper
authors: Karsten
authors: K
authors: Niehaus
authors: Dieter
authors: D
authors: Horstkotte
authors: Martin
authors: M
authors: Farr
mesh_terms: D002478:Cells, Cultured; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D003384:Coxsackievirus Infections / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D029822:Enterovirus B, Human / Q000187:drug effects* / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C107953:RAC1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D008148:Lovastatin; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein