title: Hydroxymethyl-glutaryl coenzyme a reductase inhibition limits cytomegalovirus infection in human endothelial cells.
abstract: BACKGROUND
  Statins exert anti-inflammatory effects independently of cholesterol-lowering properties. Cytomegalovirus (CMV) infection appears to be implicated in the pathophysiology of atherosclerosis by inducing inflammatory modifications in endothelial cells, especially in immunosuppressed patients. We investigated whether the activity of statins can inhibit replication of CMV in human endothelial cells.
  
  
  RESULTS
  Human umbilical vein endothelial cells (HUVECs) were infected with CMV and coincubated with fluvastatin at 0.1 and 0.2 micromol/L. Fluvastatin inhibited (P<0.001) CMV antigen expression, and this effect was dose related (P<0.001). Quantitative polymerase chain reaction showed that CMV DNA concentration was consistently lower in supernatants from fluvastatin-treated cells than in infected controls, and viral particle concentration was up to 30 times lower in 0.2 micromol/L fluvastatin-treated cells than in infected controls (10.5+/-0.9 versus 0.34+/-0.03 per 10(3) pfu/mL, P<0.001). Addition of mevalonate to treated cultures almost completely abolished fluvastatin inhibition of viral growth. Electrophoretic mobility shift assay showed that fluvastatin reduced nuclear factor-kappaB binding activity in CMV-infected cells.
  
  
  CONCLUSIONS
  HMG-CoA inhibition by fluvastatin restrains CMV replication in HUVECs by inhibiting viral antigen expression, DNA synthesis, and viral particle production, conceivably by involving a reduction of nuclear factor-kappaB binding activity.
authors.affiliation: Institute of Cardiology, University of Bologna, Bologna, Italy. lpotena@cvmed.stanford.edu
authors.forename: Luciano
authors.initials: L
authors.lastname: Potena
authors.forename: Giada
authors.initials: G
authors.lastname: Frascaroli
authors.forename: Francesco
authors.initials: F
authors.lastname: Grigioni
authors.forename: Tiziana
authors.initials: T
authors.lastname: Lazzarotto
authors.forename: Gaia
authors.initials: G
authors.lastname: Magnani
authors.forename: Luciana
authors.initials: L
authors.lastname: Tomasi
authors.forename: Fabio
authors.initials: F
authors.lastname: Coccolo
authors.forename: Liliana
authors.initials: L
authors.lastname: Gabrielli
authors.forename: Carlo
authors.initials: C
authors.lastname: Magelli
authors.forename: Maria P
authors.initials: MP
authors.lastname: Landini
authors.forename: Angelo
authors.initials: A
authors.lastname: Branzi
mesh_terms: D000956:Antigens, Viral / Q000378:metabolism; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D004279:DNA, Viral / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000821:virology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D014771:Virion / Q000302:isolation & purification
chemical_list: D000956:Antigens, Viral; D004279:DNA, Viral; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D016328:NF-kappa B; D000077340:Fluvastatin