Hydroxymethyl-glutaryl coenzyme a reductase inhibition limits cytomegalovirus infection in human endothelial cells.
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.
Potena
Luciano
L
Institute of Cardiology, University of Bologna, Bologna, Italy. lpotena@cvmed.stanford.edu
Frascaroli
Giada
G
Grigioni
Francesco
F
Lazzarotto
Tiziana
T
Magnani
Gaia
G
Tomasi
Luciana
L
Coccolo
Fabio
F
Gabrielli
Liliana
L
Magelli
Carlo
C
Landini
Maria P
MP
Branzi
Angelo
A
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
D000956:Antigens, Viral; D004279:DNA, Viral; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D016328:NF-kappa B; D000077340:Fluvastatin